Stem Cell Clinic

FAQs – Ocean Springs, MS – Gulf Coast Stem Cell …

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Gulf Coast Stem Cell & Regenerative Medicine Center (GCSC&RMC) uses adipose-derived stem cells for deployment & clinical research. Early stem cell research has traditionally been associated with the controversial use of embryonic stem cells. The new focus is on non-embryonic adult mesenchymal stem cells which are found in a persons own blood, bone marrow, and fat. Most stem cell therapy centers in the world are currently using stem cells derived from bone marrow.

A recent technological breakthrough enables us to now use adipose (fat) derived stem cells. Autologous stem cells from a persons own fat are easy to harvest safely under local anesthesia and are abundant in quantities up to 2500 times those seen in bone marrow.

Clinical success and favorable outcomes appear to be related directly to the quantity of stem cells deployed. Once these adipose-derived stem cells are administered back into the patient, they have the potential to repair human tissue by forming new cells of mesenchymal origin, such as cartilage, bone, ligaments, tendons, nerve, fat, muscle, blood vessels, and certain internal organs. Stem cells ability to form cartilage and bone makes them potentially highly effective therapy for degenerative orthopedic conditions. Their ability to form new blood vessels and smooth muscle makes them potentially very useful in treating Peyronies disease and impotence. Stem cells are used extensively in Europe and Asia to treat these conditions.

We have anecdotal and experimental evidence that stem cell therapy is effective in healing and regeneration. Stem cells seek out damaged tissues in order to repair the body naturally. The literature and internet are full of successful testimonials but we are still awaiting definitive studies demonstrating the efficacy of stem cell therapy. Such data may take five or ten years to accumulate. In an effort to provide relief for patients suffering from certain degenerative diseases that have been resistant to common modalities of medical care, we are initiating pilot studies as experimental tests of therapy effectiveness with very high numbers of adipose-derived stem cells obtained from fat. Adipose fat is an abundant and reliable source of stem cells.

GCSC&RMCs cell harvesting and isolation techniques are based on technology from Korea. This new technological breakthrough allows patients to safely receive their own autologous stem cells in extremely large quantities. Our therapy and research are patient funded and we have endeavored successfully to make it affordable. All of our sterile procedures are non-invasive and done under local anesthesia. Patients who are looking for non-surgical alternatives to their degenerative disorders can participate in our trials by filling out our application to determine if they are candidates.GCSC&RMC is proud to be state of the art in the new field of Regenerative Medicine. RETURN TO TOP

We are currently in the process of setting up FDA approved protocols for stem cell banking in collaboration with a reputable cryo-technology company. This enables a person to receive autologous stem cells at any time in the future without having to undergo liposuction which may be inconvenient or contraindicated. Having your own stem cells available for medical immediate use is a valuable medical asset.

Provisions are nearly in place for this option and storage of your own stem cells obtained by liposuction at GCSC&RMC or from fat obtained from cosmetic procedures performed elsewhere should be possible in the near future. RETURN TO TOP

Adult (NonEmbryonic) Mesenchymal Stem Cells are undifferentiated cells that have the ability to replace dying cells and regenerate damaged tissue. These special cells seek out areas of injury, disease, and destruction where they are capable of regenerating healthy cells and enabling a persons natural healing processes to be accelerated. As we gain a deeper understanding of their medical function and apply this knowledge, we are realizing their enormous therapeutic potential to help the body heal itself. Adult stem cells have been used for a variety of medicaltherapies to repair and regenerate acute and chronically damaged tissues in humans and animals. The use of stem cells is not FDA approved for treating any specific disease in the United States at this time and their use is therefore investigational. Many reputable international centers have been using stem cell therapy to treat various chronic degenerative conditions as diverse as severe neurologic diseases, renal failure, erectile dysfunction, degenerative orthopedic problems, and even cardiac and pulmonary diseases to name a few. Adult stem cells appear to be particularly effective at repairing cartilage in degenerated joints. RETURN TO TOP

Regenerative Medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to damage, or congenital defects. This field holds the promise of regenerating damaged tissues and organs in the body by stimulating previously irreparable organs to heal themselves. (Wikipedia) RETURN TO TOP

Traditionally, we have used various medications and hormones to limit disease and help the body repair itself. For example, hormone replacement therapy has, in many cases, shown the ability to more optimally help the immune system and thus help us repair diseased or injured tissues. Genetic research is an evolving area where we will eventually learn and utilize more ways of specifically dealing with gene defects causing degenerative disease. Stem cell therapy is another rapidly evolving and exciting area that has already shown considerable promise in treating many degenerative conditions. RETURN TO TOP

A stem cell is basically any cell that can replicate and differentiate. This means the cell can not only multiply, it can turn into different types of tissues. There are different kinds of stem cells. Most people are familiar with or have heard the term embryonic stem cell. These are cells from the embryonic stage that have yet to differentiate as such, they can change into any body part at all. These are then called pluripotential cells. Because they are taken from unborn or unwanted embryos, there has been considerable controversy surrounding their use. Also, while they have been used in some areas of medicine particularly, outside the United States they have also been associated with occasional tumor (teratoma) formations. There is work being conducted by several companies to isolate particular lines of embryonic stem cells for future use.

Another kind of stem cell is the adult stem cell. This is a stem cell that already resides in ones body within different tissues. In recent times, much work has been done isolating bone-marrow derived stem cells. These are also known as mesenchymal stem cells because they come from the mesodermal section of your body. They can differentiate into bone and cartilage, and probably all other mesodermal elements, such as fat, connective tissue, blood vessels, muscle and nerve tissue. Bone marrow stem cells can be extracted and because they are low in numbers, they are usually cultured in order to multiply their numbers for future use. As it turns out, fat is also loaded with mesenchymal stem cells. In fact, it has hundreds if not thousands of times more stem cells compared to bone marrow. Today, we actually have tools that allow us to separate the stem cells from fat. Because most people have adequate fat supplies and the numbers of stem cells are so great, there is no need to culture the cells over a period of days and they can be used right away. RETURN TO TOP

These adult stem cells are known as progenitor cells. This means they remain dormant (do nothing) unless they witness some level of tissue injury. Its the tissue injury that turns them on. So, when a person has a degenerative type problem, the stem cells tend to go to that area of need and stimulate the healing process. Were still not sure if they simply change into the type of injured tissue needed for repair or if they send out signals that induce the repair by some other mechanism. Suffice it to say that there are multiple animal models and a plethora of human evidence that indicates these are significant reparative cells. RETURN TO TOP

This will depend on the type of degenerative condition you have. A specialist will evaluate you and discuss whether youre a potential candidate for stem cell therapy. If after youve been recommended for therapy, had an opportunity to understand the potential risks and benefits, and decided on your own that you would like to explore this avenue, then you can be considered for stem cell therapy. Of course, even though its a minimally invasive procedure, you will still need to be medically cleared for the procedure. RETURN TO TOP

NO. However, GCSC&RMCs procedures fall under the category of physicians practice of medicine, wherein the physician and patient are free to consider their chosen course for medical care. The FDA does have guidelines about therapy and manipulation of a patients own tissues. At GCSC&RMC we meet these guidelines by providing same day deployment with the patients own cells that undergo very minimal manipulation and are inserted during the same procedure. RETURN TO TOP

No. Only adult mesenchymal stem cells are used. These cells are capable of forming bone, cartilage, fat, muscle, ligaments, blood vessels, and certain organs. Embryonic stem cells are associated with ethical considerations and limitations. RETURN TO TOP

Patients suffer from many varieties of degenerative illnesses. There may be conditions associated with nearly all aspects of the body. Board-certified specialists are ideal to evaluate, recommend and/or treat, and subsequently, follow your progress. Together, through the GCSC&RMC, we work to coordinate and provide therapy mainly with your own stem cells, but also through other avenues of regenerative medicine. This could include hormone replacement therapy or other appropriate recommendations.

For example, if you have a knee problem, you would see GCSC&RMCs Board Certified orthopedic surgeon rather than a generic clinic director. Also, you might be recommended for evaluation for hormone replacement therapy or an exercise program should such be considered optimal. Nonetheless, we believe stem cell therapy to be the likely foundation for regenerative medicine. It should also be noted, that all therapies are currently in the investigational stage. While we recognize our patients are seeking improvement in their condition through stem cell therapy, each deployment is part of an ongoing investigation to establish optimal parameters for future therapies, to evaluate for effectiveness and for any adverse effects. It is essential that patients understand they are participating in these investigational (research) analyses. Once sufficient information is appropriately documented and statistically significant, then data (validated by an Institutional Review Board) may be presented to the FDA for consideration of making an actual claim. RETURN TO TOP

Urology, cosmetic surgery, ear, nose, & throat, orthopedics, internal medicine, and cardiology are represented. Plans are currently being made for a number of other specialties. GCSC&RMC is the first multi-specialty stem cell center in the United States. RETURN TO TOP

Many have been told that they require surgery or other risky procedures for their ailments and are looking for non-invasive options. Some have heard about the compelling testimonials about stem cells in the literature and on various websites. Many have read about the results of stem cell therapy in animal models and in humans. GCSC&RMC gives a choice to those informed patients who seek modern regenerative therapy but desire convenience, quality, and affordability. GCSC&RMC fills a need for those patients who have been told that they have to travel to different countries and pay as much as twenty to one hundred thousand dollars for stem cell therapy offshore. (See stem cell tourism). RETURN TO TOP

Stem cells are harvested and deployed during the same procedure. Our patients undergo a minimally-invasive liposuction type of harvesting procedure by a qualified surgeon in our facility in Ocean Springs, Mississippi. The harvesting procedure generally lasts a few minutes and can be done under local anesthesia. Cells are then processed and are ready for deployment within 90 minutes or less. RETURN TO TOP

Bone marrow sampling (a somewhat uncomfortable procedure) yields approximately 5,000 60,000 cells that are then cultured over several days to perhaps a few million cells prior to deployment (injection into the patient). Recent advances in stem cell science have made it possible to obtain high numbers of very excellent quality multi-potent (able to form numerous other tissues) cells from a persons own liposuction fat. GCSC&RMC uses technology acquired from Asia to process this fat to yield approximately five hundred thousand to one million stem cells per cc of fat, and therefore, it is possible to obtain as many as 10 to 40 million cells from a single procedure. These adipose-derived stem cells can form many different types of cells when deployed properly including bone, cartilage, tendon (connective tissue), muscle, blood vessels, nerve tissue and others. RETURN TO TOP

GCSC&RMC patients have their fat (usually abdominal) harvested in our special sterile facility under a local anesthetic. The fat removal procedure lasts approximately twenty minutes. Specially designed equipment is used to harvest the fat cells and less than 100cc of fat is required. Postoperative discomfort is minimal and there is minimal restriction on activity. RETURN TO TOP

Stem cells are harvested under sterile conditions using a special closed system technology so that the cells never come into contact with the environment throughout the entire process from removal to deployment. Sterile technique and antibiotics are also used to prevent infection. RETURN TO TOP

No. Only a persons own adult autologous cells are used. These are harvested from each individual and deployed back into their own body. There is no risk of contamination or risk of introduction of mammalian DNA. RETURN TO TOP

These facilities are obtaining stem cells from bone marrow or blood in relatively small quantities and they are then culturing (growing) the cells to create adequate quantities. Research seems to indicate that the success of stem cell therapy is directly related to the quantity of cells injected. GCSC&RMC uses adipose-derived stem cells that are abundant naturally at approximately 2,500 times levels found in bone marrow (the most common source of mesenchymal stem cells). GCSC&RMC uses technology that isolates adipose stem cells in vast numbers in a short time span so that prolonged culturing is unnecessary and cells can be deployed into a patient within 90 minutes of harvesting. RETURN TO TOP

GCSC&RMC is doing pioneer research for treating many diseases. All investigational data is being collected so that results will be published in peer review literature and ultimately used to promote the advancement of cellular based regenerative medicine. FDA regulations mandate that no advertising medical claims be made and that even website testimonials are prohibited. RETURN TO TOP

No. Many are confused by this because they have heard of cancer patients receiving stem cell transplants. These patients had ablative bone marrow therapy and need stem cells to re-populate their blood and marrow. This is different from the stem cells we deploy to treat noncancerous human diseases at GCSC&RMC. RETURN TO TOP

Adult mesenchymal stem cells are not known to cause cancer. Some patients have heard of stories of cancer caused by stem cells, but these are probably related to the use of embryonic cells (Not Adult Mesenchymal Cells). These embryonic tumors known as teratomas are rare but possible occurrences when embryonic cells are used. RETURN TO TOP

Stem cell therapy is thought to be safe and not affect dormant cancers. If someone has had cancer that was treated and responded sucessfully, there is know reason to withhold stem cell deployment. In most cases, stem cells should not be used in patients with known active cancer. RETURN TO TOP

We know of no documented cases personally or in the literature where serious harm has resulted. All of our patients will be entered into a database to follow and report any adverse reactions. This information is vital to the development of stem cell science. There have been a few reports of serious complications from overseas and these are being thoroughly evaluated by epidemiologists to ascertain the facts. The International Stem Cell Society registry has over 1,000 cases currently registered and only 2% were associated with any complications, none of which were considered serious adverse events. RETURN TO TOP

None. Our aim is to make cell based medicine available to patients who are interested and to provide ongoing research data under approved Institutional Review Board (IRB) validated studies. We will follow our stem cell therapy patients over their lifetimes. This will enable us to accumulate significant data about the various degenerative diseases we treat. Instead of providing simply anecdotal or testimonial information, our goal is to categorize the various conditions and follow the patients progress through various objective (e.g. x-ray evidence or video displays) and subjective (e.g. patient and/or doctor surveys) criteria. We are aware of a lot of stories about marked improvement of a variety of conditions, but we make no claims about the intended therapy. At some point, once adequate amounts of data are accumulated, it might be appropriate to submit the information to the FDA at which point an actual claim may be substantiated and recognized by the Agency. Still, these are your own cells and not medicines for sale. They are only being used in your own body. Most likely, no claim needs to be made; rather a statistical analysis of our findings would suffice to suggest whether therapy is truly and significantly effective. We also hope to submit our patients data to an approved International Registry (See ICMS Stem Cell Registry) further fostering large collections of data to help identify both positive and negative trends. RETURN TO TOP

Our adipose derived stem cell harvesting and isolation technique yields extremely high numbers of stem cells. In reviewing outcomes data, therapy cell numbers appear to correlate with therapy success. Our cells are actually in a type of soup called Stromal Vascular Fraction SVF which is stem cells bathed in a rich mixture of natural growth factors (Not the same as human growth factor hormone which is only one type of growth factor). Some types of orthopedic and urologic diseases appear to respond better to stem cells that are super enriched with growth factors created by administering Platelet Rich Plasma to the patient. Autologous Platelet Rich Plasma is derived from a patients own blood drawn at the time of deployment. At GCSC&RMC we do not add any foreign substances or medications to the stem cells. RETURN TO TOP

Depending on the type of therapy required, stem cells can be injected through veins, arteries, into spinal fluid, subcutaneously, or directly into joints or organs. All of these are considered minimally invasive methods of introducing the stem cells. Stem cells injected intravenously are known to seek out and find (see photo) areas of tissue damage and migrate to that location thus potentially providing regenerative healing. Intravenously injected stem cells have been shown to have the capability of crossing the blood-brain barrier to enter the central nervous system and they can be identified in the patients body many months after deployment. Note yellow arrow showing the stem cells concentrated in the patients hand where he had a Dupytrens contracture (Dupuytrens contracture is a hand deformity that causes the tissue beneath the surface of the hand to thicken and contract). RETURN TO TOP

Different conditions are treated in different ways and there are different degrees of success. If the goal is regeneration of joint cartilage, one may not see expected results until several months. Some patients may not experience significant improvement and others may see dramatic regeneration of damaged tissue or resolution of disease. Many of the disorders and problems that the physicians at GCSC&RMC are treating represent pioneering work and there is a lack of data. FDA regulations prevent GCSC&RMC from making any claims about expectations for success, however, if you are chosen for therapy, it will be explained that we believe stem cell therapy may be beneficial or in some cases that we are unsure and therapy would be considered investigational. RETURN TO TOP

Stem cell therapy relies on the bodys own regenerative healing to occur. The regenerative process may take time, particularly with orthopedic patients, who may not see results for several months. In some diseases, more immediate responses are possible. RETURN TO TOP

No. Only certain medical problems are currently being treated at GCSC&RMC. Check our list or fill out a candidate application form on the website. All patients need to be medically stable enough to have the stem cell deployment in our facility. There may be some exceptional conditions that may eventually be treated in hospitalized patients, but that remains for the future. Some patients may be declined due to the severity of their problem. Other patients may not have conditions appropriate to treat or may not be covered by our specialists or our protocols. A waiting list or outside referral (if we know of someone else treating such a problem) might be applicable in such cases. RETURN TO TOP

Yes. Patients with uncontrolled cancer are excluded. If you have an active infection anywhere in your body you must be treated first. Severely ill patients may require special consideration. Also, anyone with a bleeding disorder or who takes blood thinning medications requires special evaluation before consideration for stem cells. RETURN TO TOP

The specialist seeing you at GCSC&RMC will make a determination based on your history and exam, studies, and current research findings. Any complex cases may be reviewed by our ethics advisory committee. Occasionally, we may seek opinions from thought leaders around the world. RETURN TO TOP

No. Participation in any of our protocols is not mandatory and there are no incentives, financial or otherwise, to induce patients to enroll in our studies. However, GCSC&RMC is dedicated to clinical research for the development of stem cell science. GCSC&RMC is taking an active role in cutting edge clinical research in the new field of regenerative medicine. Research studies will be explained and privacy will be maintained. Formal future research studies will be regulated by an Institutional Review Board which is an authorized agency that promotes validity, transparency and protection of human study enrollees. RETURN TO TOP

At this time, we are not treating spinal cord injuries and some advanced diseases. See list of problems currently being studied at GCSC&RMC. RETURN TO TOP

Patients who are considered to be candidates based on information provided in the candidate application form will be invited for a consultation with one of our panel physicians. $250 is charged for this consultation which includes office evaluation (but may also include physicians evaluation of X-Rays, records, or telephonic consultations). Unfortunately, insurance generally will not cover the actual cost of stem cell therapy in most cases since stem cell therapy is still considered experimental. The cost varies depending on the disease state being treated and which type of stem cell deployment is required. RETURN TO TOP

Because of recent innovations in technology, GCSC&RMC is able to provide outpatient stem cell therapy at a fraction of the cost of that seen in many overseas clinics. The fee covers fat cell harvesting, cell preparation, and stem cell deployment which may include the use of advanced interventional radiology and fluoroscopy techniques. Financing is available through a credit vendor. RETURN TO TOP

Stem cells can be cryopreserved in the form of liposuction fat for prolonged periods of time. Currently, this service is outsourced to an outside provider known to have excellent quality control. Many patients have been inquiring about banking cells while they are still young since stem cell numbers drop naturally with each decade of life and some advocate obtaining and saving cells to be used later in life as needed. (see chart). RETURN TO TOP

Most patients, especially those with orthopedic conditions, require only one deployment. Certain types of degenerative conditions, particularly auto-immune disease, may respond best to a series of stem cell deployments. The number and necessity of any additional procedures would be decided on a case by case basis. Financial consideration is given in these instances. RETURN TO TOP

A good resource is the International Cellular Medicine Society (ICMS). Stem Cells 101

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See the article here:
FAQs - Ocean Springs, MS - Gulf Coast Stem Cell ...

Hematopoietic stem cell – Wikipedia

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis.[1] This process occurs in the red bone marrow, in the core of most bones. In embryonic development, the red bone marrow is derived from the layer of the embryo called the mesoderm.

Hematopoiesis is the process by which all mature blood cells are produced. It must balance enormous production needs (more than 500 billion blood cells are produced every day) with the need to precisely regulate the number of each blood cell type in the circulation. In vertebrates, the vast majority of hematopoiesis occurs in the bone marrow and is derived from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal.

HSCs give rise to both the myeloid and lymphoid lineages of blood cells. Myeloid and lymphoid lineages both are involved in dendritic cell formation. Myeloid cells include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, and megakaryocytes to platelets. Lymphoid cells include T cells, B cells, and natural killer cells. The definition of hematopoietic stem cells has evolved since HSCs were first discovered in 1961.[2] The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. HSCs constitute 1:10.000 of cells in myeloid tissue.

HSC transplants are used in the treatment of cancers and other immune system disorders.[3]

With regard to morphology, hematopoietic stem cells resemble lymphocytes. They are non-adherent, and rounded, with a rounded nucleus and low cytoplasm-to-nucleus ratio. Since HSCs cannot be isolated as a pure population, it is not possible to identify them in a microscope.

HSCs are found in the bone marrow of adults, especially in the pelvis, femur, and sternum. They are also found in umbilical cord blood and, in small numbers, in peripheral blood.[4]

Stem and progenitor cells can be taken from the pelvis, at the iliac crest, using a needle and syringe.[5] The cells can be removed as liquid (to perform a smear to look at the cell morphology) or they can be removed via a core biopsy (to maintain the architecture or relationship of the cells to each other and to the bone).[citation needed]

In order to harvest stem cells from the circulating peripheral blood, blood donors are injected with a cytokine, such as granulocyte-colony stimulating factor (G-CSF), that induces cells to leave the bone marrow and circulate in the blood vessels.[6] In mammalian embryology, the first definitive HSCs are detected in the AGM (aorta-gonad-mesonephros), and then massively expanded in the fetal liver prior to colonising the bone marrow before birth.[7]

It was originally believed that all HSCs were alike in their self-renewal and differentiation abilities. This view was first challenged by the 2002 discovery by the Muller-Sieburg group in San Diego, who illustrated that different stem cells can show distinct repopulation patterns that are epigenetically predetermined intrinsic properties of clonal Thy-1lo Sca-1+ linc-kit+ HSC.[8][9][10] The results of these clonal studies led to the notion of lineage bias. Using the ratio = L / M {displaystyle rho =L/M} of lymphoid (L) to myeloid (M) cells in blood as a quantitative marker, the stem cell compartment can be split into three categories of HSC. Balanced (Bala) HSCs repopulate peripheral white blood cells in the same ratio of myeloid to lymphoid cells as seen in unmanipulated mice (on average about 15% myeloid and 85% lymphoid cells, or 3 10). Myeloid-biased (My-bi) HSCs give rise to very few lymphocytes resulting in ratios 0 < < 3, while lymphoid-biased (Ly-bi) HSCs generate very few myeloid cells, which results in lymphoid-to-myeloid ratios of > 10. All three types are normal types of HSC, and they do not represent stages of differentiation. Rather, these are three classes of HSC, each with an epigenetically fixed differentiation program. These studies also showed that lineage bias is not stochastically regulated or dependent on differences in environmental influence. My-bi HSC self-renew longer than balanced or Ly-bi HSC. The myeloid bias results from reduced responsiveness to the lymphopoetin interleukin 7 (IL-7).[9]

Subsequently, other groups confirmed and highlighted the original findings.[11] For example, the Eaves group confirmed in 2007 that repopulation kinetics, long-term self-renewal capacity, and My-bi and Ly-bi are stably inherited intrinsic HSC properties.[12] In 2010, the Goodell group provided additional insights about the molecular basis of lineage bias in side population (SP) SCA-1+ lin c-kit+ HSC.[13] As previously shown for IL-7 signaling, it was found that a member of the transforming growth factor family (TGF-beta) induces and inhibits the proliferation of My-bi and Ly-bi HSC, respectively.

HSCs can be identified or isolated by the use of flow cytometry where the combination of several different cell surface markers are used to separate the rare HSCs from the surrounding blood cells. HSCs lack expression of mature blood cell markers and are thus, called Lin-. Lack of expression of lineage markers is used in combination with detection of several positive cell-surface markers to isolate HSCs. In addition, HSCs are characterised by their small size and low staining with vital dyes such as rhodamine 123 (rhodamine lo) or Hoechst 33342 (side population).

The classical marker of human HSC is CD34 first described independently by Civin et al. and Tindle et al.[14][15][16][17] It is used to isolate HSC for reconstitution of patients who are haematologically incompetent as a result of chemotherapy or disease.

Many markers belong to the cluster of differentiation series, like: CD34, CD38, CD90, CD133, CD105, CD45, and also c-kit the receptor for stem cell factor.

There are many differences between the human and murine hematopoietic cell markers for the commonly accepted type of hematopoietic stem cells.[18]

However, not all stem cells are covered by these combinations that, nonetheless, have become popular. In fact, even in humans, there are hematopoietic stem cells that are CD34/CD38.[19][20] Also some later studies suggested that earliest stem cells may lack c-kit on the cell surface.[21] For human HSCs use of CD133 was one step ahead as both CD34+ and CD34 HSCs were CD133+.

Traditional purification method used to yield a reasonable purity level of mouse hematopoietic stem cells, in general, requires a large(~1012) battery of markers, most of which were surrogate markers with little functional significance, and thus partial overlap with the stem cell populations and sometimes other closely related cells that are not stem cells. Also, some of these markers (e.g., Thy1) are not conserved across mouse species, and use of markers like CD34 for HSC purification requires mice to be at least 8 weeks old.

Alternative methods that could give rise to a similar or better harvest of stem cells is an active area of research, and are presently[when?] emerging. One such method uses a signature of SLAM family cell surface molecules. The SLAM (Signaling lymphocyte activation molecule) family is a group of more than 10 molecules whose genes are located mostly tandemly in a single locus on chromosome 1 (mouse), all belonging to a subset of the immunoglobulin gene superfamily, and originally thought to be involved in T-cell stimulation. This family includes CD48, CD150, CD244, etc., CD150 being the founding member, and, thus, also known as slamF1, i.e., SLAM family member 1.

The signature SLAM codes for the hemopoietic hierarchy are:

For HSCs, CD150+CD48 was sufficient instead of CD150+CD48CD244 because CD48 is a ligand for CD244, and both would be positive only in the activated lineage-restricted progenitors. It seems that this code was more efficient than the more tedious earlier set of the large number of markers, and are also conserved across the mouse strains; however, recent work has shown that this method excludes a large number of HSCs and includes an equally large number of non-stem cells.[22][23]CD150+CD48 gave stem cell purity comparable to Thy1loSCA-1+linc-kit+ in mice.[24]

Irving Weissman's group at Stanford University was the first to isolate mouse hematopoietic stem cells in 1988Template:Purification and characterization of mouse hematopoietic stem cells. and was also the first to work out the markers to distinguish the mouse long-term (LT-HSC) and short-term (ST-HSC) hematopoietic stem cells (self-renew-capable), and the Multipotent progenitors (MPP, low or no self-renew capability the later the developmental stage of MPP, the lesser the self-renewal ability and the more of some of the markers like CD4 and CD135):

Between 1948 and 1950, the Committee for Clarification of the Nomenclature of Cells and Diseases of the Blood and Blood-forming Organs issued reports on the nomenclature of blood cells.[25][26] An overview of the terminology is shown below, from earliest to final stage of development:

The root for erythrocyte colony-forming units (CFU-E) is "rubri", for granulocyte-monocyte colony-forming units (CFU-GM) is "granulo" or "myelo" and "mono", for lympocyte colony-forming units (CFU-L) is "lympho" and for megakaryocyte colony-forming units (CFU-Meg) is "megakaryo". According to this terminology, the stages of red blood cell formation would be: rubriblast, prorubricyte, rubricyte, metarubricyte, and erythrocyte. However, the following nomenclature seems to be, at present, the most prevalent:

Osteoclasts also arise from hemopoietic cells of the monocyte/neutrophil lineage, specifically CFU-GM.

In the context of hematopoietic stem cells, a colony-forming unit is a subtype of HSC. (This sense of the term is different from colony-forming units of microbes, which is a cell counting unit.) There are various kinds of HSC colony-forming units:

The above CFUs are based on the lineage. Another CFU, the colony-forming unitspleen (CFU-S), was the basis of an in vivo clonal colony formation, which depends on the ability of infused bone marrow cells to give rise to clones of maturing hematopoietic cells in the spleens of irradiated mice after 8 to 12 days. It was used extensively in early studies, but is now considered to measure more mature progenitor or transit-amplifying cells rather than stem cells.

DNA strand breaks accumulate in long term HSCs during aging.[27] This accumulation is associated with a broad attenuation of DNA repair and response pathways that depends on HSC quiescence.[27]Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template. The NHEJ pathway depends on several proteins including ligase 4, DNA polymerase mu and NHEJ factor 1 (NHEJ1, also known as Cernunnos or XLF).

DNA ligase 4 (Lig4) has a highly specific role in the repair of double-strand breaks by NHEJ. Lig4 deficiency in the mouse causes a progressive loss of HSCs during aging.[28] Deficiency of lig4 in pluripotent stem cells results in accumulation of DNA double-strand breaks and enhanced apoptosis.[29]

In polymerase mu mutant mice, hematopoietic cell development is defective in several peripheral and bone marrow cell populations with about a 40% decrease in bone marrow cell number that includes several hematopoietic lineages.[30] Expansion potential of hematopoietic progenitor cells is also reduced. These characteristics correlate with reduced ability to repair double-strand breaks in hematopoietic tissue.

Deficiency of NHEJ factor 1 in mice leads to premature aging of hematopoietic stem cells as indicated by several lines of evidence including evidence that long-term repopulation is defective and worsens over time.[31] Using a human induced pluripotent stem cell model of NHEJ1 deficiency, it was shown that NHEJ1 has an important role in promoting survival of the primitive hematopoietic progenitors.[32] These NHEJ1 deficient cells possess a weak NHEJ1-mediated repair capacity that is apparently incapable of coping with DNA damages induced by physiological stress, normal metabolism, and ionizing radiation.[32]

The sensitivity of haematopoietic stem cells to Lig4, DNA polymerase mu and NHEJ1 deficiency suggests that NHEJ is a key determinant of the ability of stem cells to maintain themselves against physiological stress over time.[28] Rossi et al.[33] found that endogenous DNA damage accumulates with age even in wild type HSCs, and suggested that DNA damage accrual may be an important physiological mechanism of stem cell aging.

Being calm is different from doing nothing, the HSCs stay calm and maintain their quiescent nature. During the need of action it revokes the dormant state and becomes an active participant in the host metabolism. These Metabolic alteration that a stem cell undergoes during proliferation and quiescence are decisive which makes the cells to survive in extreme hypoxic environment that prevails in bone marrow.[34] This kind of quiescence nature in HSCs may be the reason behind for being/acting as stem cells for long lasting periods even throughout the lifetime of an individual.

HSCs can replenish all blood cell types (i.e., are multipotent) and self-renew. A small number of HSCs can expand to generate a very large number of daughter HSCs. This phenomenon is used in bone marrow transplantation,[35] when a small number of HSCs reconstitute the hematopoietic system. This process indicates that, subsequent to bone marrow transplantation, symmetrical cell divisions into two daughter HSCs must occur.

Stem cell self-renewal is thought to occur in the stem cell niche in the bone marrow, and it is reasonable to assume that key signals present in this niche will be important in self-renewal.[1] There is much interest in the environmental and molecular requirements for HSC self-renewal, as understanding the ability of HSC to replenish themselves will eventually allow the generation of expanded populations of HSC in vitro that can be used therapeutically.

HSCs have a higher potential than other immature blood cells to pass the bone marrow barrier, and, thus, may travel in the blood from the bone marrow in one bone to another bone. If they settle in the thymus, they may develop into T cells. In the case of fetuses and other extramedullary hematopoiesis, HSCs may also settle in the liver or spleen and develop.

This enables HSCs to be harvested directly from the blood.

A cobblestone area-forming cell (CAFC) assay is a cell culture-based empirical assay. When plated onto a confluent culture of stromal feeder layer, a fraction of HSCs creep between the gaps (even though the stromal cells are touching each other) and eventually settle between the stromal cells and the substratum (here the dish surface) or trapped in the cellular processes between the stromal cells. Emperipolesis is the in vivo phenomenon in which one cell is completely engulfed into another (e.g. thymocytes into thymic nurse cells); on the other hand, when in vitro, lymphoid lineage cells creep beneath nurse-like cells, the process is called pseudoemperipolesis. This similar phenomenon is more commonly known in the HSC field by the cell culture terminology cobble stone area-forming cells (CAFC), which means areas or clusters of cells look dull cobblestone-like under phase contrast microscopy, compared to the other HSCs, which are refractile. This happens because the cells that are floating loosely on top of the stromal cells are spherical and thus refractile. However, the cells that creep beneath the stromal cells are flattened and, thus, not refractile. The mechanism of pseudoemperipolesis is only recently coming to light. It may be mediated by interaction through CXCR4 (CD184) the receptor for CXC Chemokines (e.g., SDF1) and 41 integrins.[36]

Hematopoietic stem cells (HSC) cannot be easily observed directly, and, therefore, their behaviors need to be inferred indirectly. Clonal studies are likely the closest technique for single cell in vivo studies of HSC. Here, sophisticated experimental and statistical methods are used to ascertain that, with a high probability, a single HSC is contained in a transplant administered to a lethally irradiated host. The clonal expansion of this stem cell can then be observed over time by monitoring the percent donor-type cells in blood as the host is reconstituted. The resulting time series is defined as the repopulation kinetic of the HSC.

The reconstitution kinetics are very heterogeneous. However, using symbolic dynamics, one can show that they fall into a limited number of classes.[37] To prove this, several hundred experimental repopulation kinetics from clonal Thy-1lo SCA-1+ lin c-kit+ HSC were translated into symbolic sequences by assigning the symbols "+", "-", "~" whenever two successive measurements of the percent donor-type cells have a positive, negative, or unchanged slope, respectively. By using the Hamming distance, the repopulation patterns were subjected to cluster analysis yielding 16 distinct groups of kinetics. To finish the empirical proof, the Laplace add-one approach[clarification needed] was used to determine that the probability of finding kinetics not contained in these 16 groups is very small. By corollary, this result shows that the hematopoietic stem cell compartment is also heterogeneous by dynamical criteria.

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Hematopoietic stem cell - Wikipedia