Induced Pluripotent Stem Cells – cellapplications.com

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Human Induced Pluripotent Stem Cells (HiPSC) Top: HiPSC express pluriotency markers OCT4, Nanog, LIN28 and SSEA-4. Bottom: HiPSC differentiate into cell derivatives from the 3 embryonic layers: Neuronal marker beta III tubulin (TUJ1), Smooth Muscle Actin (SMA) and Hepatocyte Nuclear Factor 3 Beta (HNF3b).

Cell Applications, Inc. has a deep, rich history in HiPSC

Human Dermal Fibroblasts (HDF) from Cell Applications were used by Nobel Laureate S. Yamanaka to establish iPSC in his groundbreaking publications in 2007, unleashing a revolution in stem cell biology. Yamanaka and collaborators demonstrated that expression of four transcription factors widely prevalent in embryonic stem cells is sufficient to trigger the transition of somatic cells towards a pluripotent state that resembles embryonic stem cells in many aspects, such as the expression of classic pluripotency markers and the ability to generate cell derivatives from the three embryonic germ layers.

HiPSC are generated from somatic cells, eliminating ethical considerations associated with scientific work based on embryonic stem cells. Furthermore, being donor/patient-specific, they open possibilities for a wide variety of studies in biomedical research. Donor somatic cells carry the genetic makeup of the diseased patient, hence HiPSC can be used directly to model disease on a dish.

Thus, one of the main uses of HiPSC has been in genetic disease modeling in organs and tissues, such as the brain (Alzheimers, Autism Spectrum Disorders), heart (Familial Hypertrophic, Dilated, and Arrhythmogenic Right Ventricular Cardiomyopathies), and skeletal muscle (Amyotrophic Lateral Sclerosis, Spinal Muscle Atrophy). The combination of HiPSC technology and gene editing strategies such as the CRISPR/Cas9 system creates a powerful platform in which disease-causing mutations can be created on demand and sets of isogenic cell lines (with and without mutations) serve as convenient tools for disease modeling studies.

Other applications of HiPSC and iPSC-differentiated cells include drug screening, development, efficacy and toxicity assessment. As an example, through the FDA-backed CiPA (Comprehensive in vitro Pro-Arrhythmia Assessment) initiative, HiPSC-derived cardiac muscle cells (cardiomyocytes) are poised to constitute a new standard model for the evaluation of cardiotoxicity of new drugs, which is the main reason of drug withdrawal from the market. Finally, HiPSC-differentiated cells are being used in early stage technology development for applications in regenerative medicine. Bio-printing and tissue constructs have also been considered as attractive applications for HiPSC.

StemoniX

Our partner StemoniX is a cutting-edge biotechnology company that is leading the development and manufacturing of HiPSC. They generate biologically accurate miniaturized organ microtissue for academic and industrial pharmaceutical research and discovery. StemoniX, a licensee of Academia Japans iPS patent portfolio, provides high quality HiPSC cells to researchers around the world. StemoniX HiPSC are thoroughly characterized for pluripotency with established pluripotency markers. Proven technology incorporating the latest innovations is able to provide cardiomyocytes with in vitro-like features. Confirmative tests show the HiPSC differentiate into derivatives from the 3 embryonic layers.

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Induced Pluripotent Stem Cells - cellapplications.com

Induced pluripotent stem cell models from X-linked …

Objective:

Because of a lack of an appropriate animal model system and the inaccessibility of human oligodendrocytes in vivo, X-linked adrenoleukodystrophy (X-ALD)-induced pluripotent stem cells (iPSCs) would provide a unique cellular model for studying etiopathophysiology and development of therapeutics for X-ALD.

We generated and characterized iPSCs of the 2 major types of X-ALD, childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN), and differentiated them into oligodendrocytes and neurons. We evaluated disease-relevant phenotypes by pharmacological and genetic approaches.

We established iPSCs from the patients with CCALD and AMN. Both CCALD and AMN iPSCs normally differentiated into oligodendrocytes, the cell type primarily affected in the X-ALD brain, indicating no developmental defect due to the ABCD1 mutations. Although low in X-ALD iPSCs, very long chain fatty acid (VLCFA) level was significantly increased after oligodendrocyte differentiation. VLCFA accumulation was much higher in CCALD oligodendrocytes than AMN oligodendrocytes but was not significantly different between CCALD and AMN neurons, indicating that the severe clinical manifestations in CCALD might be associated with abnormal VLCFA accumulation in oligodendrocytes. Furthermore, the abnormal accumulation of VLCFA in the X-ALD oligodendrocytes can be reduced by the upregulated ABCD2 gene expression after treatment with lovastatin or 4-phenylbutyrate.

X-ALD iPSC model recapitulates the key events of disease development (ie, VLCFA accumulation in oligodendrocytes), provides new clues for better understanding of the disease, and allows for early and accurate diagnosis of the disease subtypes. X-ALD oligodendrocytes can be a useful cell model system to develop new therapeutics for treating X-ALD. ANN NEUROL 2011;

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Induced pluripotent stem cell models from X-linked ...

Medi-Cal: Medi-Cal Update – Clinics and Hospitals | May …

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Effective retroactively for dates of service on or after November 1, 2015, reimbursement for factor X preparations requires a separate Service Authorization Request (SAR) for the California Children's Services (CCS)/Genetically Handicapped Persons Program (GHPP).

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, the current HCPCS Local Level III codes for Home Health Agencies (HHA) will be discontinued. The codes will be replaced by 11 new Health Insurance Portability and Accountability Act (HIPAA) compliant national and revenue codes. The HCPCS national code and revenue code will be required on all home health claims.

Every new Treatment Authorization Request (TAR) and electronic TAR (eTAR) submitted with dates of service on or after June 1, 2016, must include the HCPCS codes described below; the revenue code is not required. The Department of Health Care Services (DHCS) will provide directions at regular intervals, reminding providers to exhaust existing TARs and Service Authorization Requests (SARs).

Providers should review their inventory for previously approved TARs with HHA services that have dates of service on or after June 1, 2016. For those TARs, providers must submit a new TAR or eTAR with the appropriate HCPCS code to cover any remaining service period on or after June 1, 2016.

If the submitted TAR is for the purpose of updating the codes for the same authorization period, it will not be reviewed for medical necessity.

The conversion is as follows:

Includes supplies that are used as part of the treatment visit.

No limit on the number of daily visits.

Limited to 40 15-minute increments per day

Limited to one visit per day or four 15-minute increments.

Limited to one visit per day or four 15-minute increments.

Limited to one visit per day or four 15-minute increments.

Limited to one visit per day or four 15-minute increments.

Respiratory therapist services can be authorized and billed under 99600.

CPT-4 code 99502 Home visit for newborn care and assessment

Does not require a TAR.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after April 1, 2016, the following diabetes self-management training (DSMT) HCPCS codes are Medi-Cal benefits:

The frequency restrictions for claims paid in the first continuous 12 months (one year) and subsequent years have been updated in the provider manual.

Claims with additional number of hours are to be billed with a Treatment Authorization Request (TAR), California Children's Services (CCS)/Genetically Handicapped Persons Program (GHPP) stamp or CCS Service Authorization Request (SAR).

HCPCS codes G0108 and G0109 may not be billed on the same date of service as CPT-4 codes 97802 97804.

Effective for dates of service on or after April 1, 2016, the following medical nutrition therapy (MNT) CPT-4 codes are Medi-Cal benefits:

Claims with additional number of hours are to be billed with a TAR, CSS/GHPP stamp, or CCS SAR.

CPT-4 codes 97802 97804 may not be billed on the same date of service as HCPCS codes G0108 and G0109.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, genetic testing for maturity onset diabetes of the young (MODY) is reimbursable under the following CPT-4 codes as a new Medi-Cal benefit:

Reimbursement for MODY requires an approved Treatment Authorization Request (TAR) and requires providers to document the following on the TAR:

This information is reflected in the following provider manual(s):

Effective retroactively for dates of service on or after October 1, 2015, select HCPCS and CPT-4 codes are no longer split billable. Claim lines with the following codes must not be billed with modifiers 26, TC or 99, and do not require a modifier:

This information is reflected in the following provider manual(s):

Effective retroactively for dates of service on or after September 1, 2012, policy language and billing instructions are updated in the provider manual for Healthcare Common Procedure System (HCPCS) codes J1950 (injection, leuprolide acetate [for depot suspension], per 3.75 mg) and J9217 (leuprolide acetate [for depot suspension], 7.5 mg).

For claims denied with dates of service on or after September 1, 2012, providers may submit new claims for denials due to incorrect coding of HCPCS codes J1950 or J9217. Providers may also submit new claims for denials due to incorrect billing with J9217 in place of J1950 or vice versa. To initiate a new claim, providers must submit a Claims Inquiry Form (CIF) to void the previously denied claim. Both the CIF and new claim must be submitted together.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after January 1, 2016, HCPCS code J9299 (injection, nivolumab, 1 mg) replaces terminated HCPCS code C9453 (injection, nivolumab, 1 mg). The following are indications for the treatment of patients 18 years of age and older:

Recommended dosage instructions vary dependent upon the administration combination with ipilimumab.

The code requires an approved Treatment Authorization Request (TAR). Affected claims will be reprocessed.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, policy for HCPCS code J9047 (injection, carfilzomib, 1 mg) has been updated.

Carfilzomib is indicated for the treatment of multiple myeloma and is limited to patients 18 years of age and older.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after July 1, 2016, HCPCS codes C9137 (injection, factor VIII [antihemophilic factor, recombinant] PEGylated, 1 I.U.) and C9138 (injection, factor VIII [antihemophilic factor, recombinant] [Nuwiq], 1 I.U.) are Medi-Cal benefits. To bill for injection, factor VIII or injection, factor VIII (Nuqwiq), providers should now use codes C9137 and C9138, respectively, instead of HCPCS code J7199 (hemophilia clotting factor, not otherwise classified).

This information is reflected in the following provider manual(s):

Effective January 1, 2016, through December 31, 2016, Presumptive Eligibility (PE) for Pregnant Women providers must use the following income eligibility guidelines to make PE for Pregnant Women determinations.

This information is reflected in the following provider manual(s):

The Department of Health Care Services (DHCS) identified a claims processing issue causing claims billed with the following CPT-4 codes to deny when billed in conjunction with ICD-10-CM diagnosis codes O09.521 O09.523 (supervision of elderly multigravida):

This issue affects claims with dates of service on or after October 1, 2015.

DHCS will notify providers when the issue is resolved. Providers should continue to submit claims timely. Affected claims will be reprocessed via an Erroneous Payment Correction (EPC). Providers are encouraged to check the Medi-Cal website regularly for updates regarding this issue.

An article in the February 2016 Medi-Cal Update announced that, effective for dates of service on or after March 1, 2016, reimbursement for screening mammograms is restricted to females 50 to 74 years of age. This announcement was not compliant with the Consolidated Appropriations Act of 2016 (House Resolution 2029).

Providers should continue to supply mammography services. Breast cancer screening mammography for females 40 years of age and older, by any provider, once a year is reimbursable.

Retroactive to September 1, 2013, Medi-Cal's policy on reimbursement for screening mammograms is consistent with the U.S. Preventive Services Task Force's 2002 recommendation of breast cancer screening mammography every year for women 40 years of age and older. The revised policy applies to the following codes:

There are no diagnostic restrictions for screening mammograms. An approved Treatment Authorization Request (TAR) may override gender restrictions. Providers should continue to submit claims timely.

Denied claims for males for codes 77052, 77057 and G0202 will be reviewed retroactive to September 1, 2013. If authorization was documented, these claims will be reprocessed through the Erroneous Payment Correction (EPC) process.

Providers should continue to check the Medi-Cal website regularly for updates.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, CPT-4 codes 81519 (oncology [breast], mRNA, gene expression profiling by real-time RT-PCR of 21 genes, utilizing formalin-fixed paraffin embedded tissue, algorithm reported as recurrence score) and 81599 (unlisted multinalyte assay with algorithmic analysis) are Medi-Cal benefits.

Codes 81519 and 81599 have a frequency limit of once in a lifetime and require a Treatment Authorization Request (TAR) with documentation of the following:

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, a sterilization Consent Form (PM 330) and an approved Treatment Authorization Request (TAR) are required for the following CPT-4 codes, when the procedure will result in sterilization:

For all procedures that ensure sterilization, including unilateral procedures for patients who only have one ovary, testicle or vas, a PM 330 is required. Additional information about requirements for these procedures is located in the Sterilization section of the Part 2 provider manual.

This information is reflected in the following provider manual(s):

Bayer Corporation acquired Conceptus in 2013. Bayer provides the Essure System ESS305, a micro-insert procedure billed under CPT-4 code 58565 (hysteroscopy, surgical; with bilateral fallopian tube cannulation to induce occlusion by placement of permanent implants).

This information is reflected in the following provider manual(s):

Effective for dates of service on or after April 1, 2016, HCPCS code C9461 (choline C 11, diagnostic, per study dose) is a new Medi-Cal benefit. Allowable modifiers are 99 and U7. An invoice is required for reimbursement.

This information is reflected in the following provider manual(s):

Providers are encouraged to access the California Department of Public Healths (CDPH) Zika Web page, which continues to publish updates about Zika virus. Some of the available resources include Zika Virus FAQs for Health Care Providers, a Zika Questions and Answers fact sheet for the general public and a colorful, ready-to-print Zika and Pregnancy poster. Some resources are also available in Spanish.

CDPH asks that providers and their staff #TalkZIKA by sharing and retweeting social media messages. Providers can follow CDPH on Facebook (English and Spanish pages) and Twitter. In addition, providers can promote and provide Zika facts by adding the following clickable graphic to their email signatures, by simply copying the graphic and pasting using the Keep Source Formatting option. Clicking the image opens the CDPH Zika Web page.

Effective for dates of service on or after June 1, 2016, reimbursement for hormone injections used in the treatment of malignant neoplasms does not require an ICD-10-CM diagnosis code.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, the Department of Health Care Services (DHCS) has updated the Treatment Authorization Request (TAR) requirement for bariatric surgery. This procedure is no longer required to be performed in a Centers for Medicare and Medicaid Services (CMS) certified Center of Excellence (COE).

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, liver-lung and liver-heart transplants are Medi-Cal benefits. In order to be reimbursable for liver-lung and liver-heart transplantation, the institution must be a Medi-Cal approved Center of Excellence for liver-lung and liver-heart transplants.

Policy Updates for Liver Transplantations

Indications for Liver-Heart and Liver-Lung Transplants

This information is reflected in the following provider manual(s):

Effective retroactively for dates of service on or after November 1, 2014, rates for the following codes have changed:

An Erroneous Payment Correction (EPC) will be implemented to reprocess affected claims.

Effective retroactively for dates of service on or after September 1, 2014, providers billing for CPT-4 code 29125 (application of short arm splint; static) are no longer required to submit an attachment for reimbursement. Providers should bill CPT-4 code 29125 with modifier AG (primary surgeon), SA (nurse practitioner rendering service in collaboration with a physician) or U7 (services rendered by physician assistant) to indicate their provider type.

An Erroneous Payment Correction will be implemented to reprocess affected claims.

A new DUR Educational Article titled Drug Safety Communication: Saxagliptin, Alogliptin and Risk of Heart Failure (PDF format) is available on the DUR: Educational Articles page of the Medi-Cal website.

A new DUR Educational Article titled Clinical Review: Atypical Antipsychotics and Adverse Metabolic Effects (PDF format) is available on the DUR: Educational Articles page of the Medi-Cal website.

A new DUR Educational Article titled Drug Safety Communication: New Safety Warnings Added to Prescription Opioids (PDF format) is available on the DUR: Educational Articles page of the Medi-Cal website.

Effective immediately, unless otherwise directed by Medi-Cal, all paper Treatment Authorization Requests (TARs) should be sent to the following location:

TAR Processing Center 820 Stillwater Road West Sacramento, CA 95605-1630

If a provider submits a TAR to a field office, the TAR will be returned to the provider with instructions to send the TAR to the TAR Processing Center.

For TAR status or issues, providers may call the Telephone Service Center (TSC) at 1-800-541-5555. Providers outside of California may call (916) 636-1980.

Department of Health Care Services (DHCS) offers the Provider Manual on the Medi-Cal website in Microsoft Word format and as a ZIP (compressed file). The website also contains links to free software to view these file formats.

DHCS is exploring modernizing the Medi-Cal, Child Health and Disability Prevention (CHDP) and Family Planning, Access, Care and Treatment (Family PACT) provider manuals to reflect the shift to mobile computing.

This Provider Manual Survey will collect provider feedback on this modernization effort. Responses will help DHCS assess provider concerns about moving toward a more mobile-friendly platform. While participation is not required, DHCS encourages all providers to take the survey. All answered surveys will be kept confidential and anonymous.

The Medi-Cal and specialty program provider manuals include online indexes that assist providers in finding information in the provider manuals. The Medi-Cal website also includes an online search tool that allows providers to quickly search key words and locate appropriate policy information in the provider manuals.

The Department of Health Care Services (DHCS) is exploring an idea to retire the index sections from the Medi-Cal, Child Health and Disability Prevention (CHDP) and Family Planning, Access, Care and Treatment (Family PACT) provider manuals.

DHCS developed the Manual Indexes Survey to collect provider feedback. Responses will help DHCS assess any provider issues or concerns about retiring the indexes. While participation is not required, DHCS encourages all providers to take the survey. All answered surveys will be kept confidential and anonymous.

Providers should note an Acronyms and Abbreviations Glossary section will remain in the provider manuals to assist providers with acronyms, and the Medi-Cal website's search function will still be available for provider use.

Effective for dates of service on or after January 1, 2016, the Medi-Cal claims processing system has been updated to align medical transportation and physician administered drug codes to the National Correct Coding Initiative (NCCI) edits regarding Medically Unlikely Edits (MUEs).

For additional information on NCCI MUEs, providers may refer to the Medically Unlikely Edits page of the Centers for Medicare & Medicaid Services (CMS) website.

The Centers for Medicare & Medicaid Services (CMS) has released the quarterly National Correct Coding Initiative (NCCI) payment policy updates. These mandatory national edits have been incorporated into the Medi-Cal claims processing system and are valid for dates of service on or after April 1, 2016.

For additional information, refer to The National Correct Coding Initiative in Medicaid page of the Medicaid website.

Beginning June 7, 2016, and continuing throughout the month of June, the Department of Health Care Services (DHCS) Fiscal Intermediary, Xerox State Healthcare, LLC (Xerox) invites providers to participate in Medi-Cal provider training webinars. The webinars will be:

Providers will also have the ability to print class materials and ask questions during the training sessions. For those who are unable to attend, all recorded webinars will be archived and made available for viewing on the MLP.

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Medi-Cal: Medi-Cal Update - Clinics and Hospitals | May ...

Generation of germline-competent induced pluripotent stem …

We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.

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Generation of germline-competent induced pluripotent stem ...

Platelet Rich Plasma Therapy and Osteoarthritis – PRP …

Recently, emerging evidence has suggested that Platelet Rich Plasma (PRP) may also be of assistance in the treatment of osteoarthritis and other degenerative conditions of joints. It is felt that the growth factors may assist in cartilage regeneration and also mediate benefit by providing an immune modulating effect, whereby the inflammatory cascade is dampened. Thus, PRP may act as a natural anti-inflammatory substance to result in symptomatic pain relief of sore arthritic joints.

The process of obtaining PRP for use in treatment of osteoarthritis of joints is identical to that outlined for PRP injections of tendons.

Patients and referring clinicians may have recently become aware of this procedure in the media: (ACA "New Knees", Friday, August 30, 2013 - http://aca.ninemsn.com.au/article.aspx?id=8715252) and may therefore find our fact sheet on PRP injections of further assistance.

An ultrasound machine is used to guide the safe and accurate delivery of PRP into a patients arthritic knee.

For more information read: Melbourne Radiology Clinic - Patient Fact Sheet: Autologous Blood Injection & Platelet Rich Plasma Injections

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Platelet Rich Plasma Therapy and Osteoarthritis - PRP ...

Induced pluripotent stem-cell therapy – Wikipedia

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle-cell anemia. Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.[citation needed]

Sickle-cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle-cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, "the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels".[5]

Researchers examined "the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing."[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that "all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice."[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

In the future, researchers hope that induced pluripotent cells may be used to treat other diseases. Pluripotency is a crucial part of disease treatment because iPS cells are capable of differentiation in a way that is very similar to embryonic stem cells which can grow into fully differentiated tissues. iPS cells also demonstrate high telomerase activity and express human telomerase reverse transcriptase, a necessary component in the telomerase protein complex. Also, iPS cells expressed cell surface antigenic markers expressed on ES cells. Also, doubling time and mitotic activity are cornerstones of ES cells, as stem cells must self-renew as part of their definition. As said, iPS cells are morphologically similar to embryonic stem cells. Each cell has a round shape, a large nucleolus and a small amount of cytoplasm. One day, the process may be used in practical settings to provide a fundamental way of regeneration.

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Induced pluripotent stem-cell therapy - Wikipedia

Platelet Rich Plasma – L.A. Beauty Skin Center

Is your skin tone simply not as healthy and smooth as on previous occasions? Have you noted fine lines and sagging skin around your eyes, cheeks and mouth? Are you conscious of the puffiness and dark circles below your eyes? The best recommended solution to these types of skin issues is Platelet Rich Plasma therapy. PRP is an advanced treatment technology that utilizes ingredients present in an individuals blood in order to regenerate their skin and revitalize collagen, leading to healthy, young looking skin.

Platelet Rich Plasma has a protracted history of being applied in dentistry, reconstructive surgery and orthopedic medicine. Today, it is also being used in other branches of medicine including dermatology, cosmetic facial rejuvenation and skin wound healing. Scientific studies ever since have proven that PRP generates new collagen when infused into the skin and recent studies reveal that PRP can ease sun damage as well as aging skin problems.

PRP is basically a natural product produced from your own body. Through a simple blood draw, a little amount of blood is drawn from an individual into a sterile tube. Using a unique centrifuge machine, the blood is spun down in order to take out and concentrate the stem cells, growth factors and platelets that are very important for tissue healing. This little amount of blood with a high concentration of platelets and growth factors is referred to as Platelet Rich Plasma (PRP).

PRP is best known for its wonderful act of skin rejuvenation. When PRP is injected into particular parts of the skin, its high platelet concentration functions as a matrix that stimulates the growth of new collagen, revitalizes skin tissue and hence leads to a naturally smooth and firm skin. As a result, PRP treatment gets rid of wrinkles and creates a smoother skin feel and tone.

There is a huge difference between PRP therapy and other skin injections of fillers. Most fillers including Juvederm and Restylane are composed of solid material which fills skin lines and folds. They often last for short period of time and require repeated treatments to seal the area yet again. On the other hand, PRP fuels collagen growth for absolute facial rejuvenation instead of individual wrinkle enhancement. Platelet Rich Plasma therapy is recommended for faces that appear drawn, to soften below eye puffiness, enhance the overall skin tone, texture and tightness and seal skin areas where fillers are not able to reach. Fillers such as Juvederm and Restylane can be applied together with PRP given that the two forms of skin treatment actually serve different purposes. The fillers will fill particular wrinkles while PRP will enhance overall wrinkle improvement.

There is enough evidence to show that Platelet Rich Plasma can be used to treat several skin issues such as Diabetic foot ulcers, bedsores, thermal burns, hair loss, superficial and surgical injuries and skin graft donor sites. Others include facial rejuvenation and post-traumatic scars.

For optimal results, LA Beauty Skin Center is the best place to have your PRP cosmetic treatment. Improvement of the skin tone and elasticity will be visible immediately after treatment. To maintain your skin and face looking young, make follow-up PRP treatments at LA Beauty Skin Center.

Current Price

Full Face + micro needling $950

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Platelet Rich Plasma - L.A. Beauty Skin Center

Cell-treatment Home

Cell-treatment.net is a domain which I- your editor Fas Kuiters- has owned from quite some time. Since 2009 I believe.

The primary purpose of ownership of the domain name at the time- and still is- is, to describe the developments in the Regenerative Medicine world, which for me is congruent to the developments in the world of Adult Stem Cell Therapy.

The predecessor of Cell-treatment.net was online for about 4 years, until I decided to take the website off-line in 2013, since things did not go very well in the industry and the developments for the core target group, I was aiming at, at the time- patients looking for relief and cures & the general public interested in the plight of those patients- were kind of chaotic in view of regulatory agencies around the world trying to establish their footing with those regulatory frameworks.

We are now end July 2016 whilst I write these words and I can see progress and if you like, "light" at the end of the tunnel all across the Globe in respect of those regulatory procedings.

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Cell-treatment Home

Generation of Neural Crest-Like Cells From Human …

Neural crest cells (NCC) hold great promise for tissue engineering, however the inability to easily obtain large numbers of NCC is a major factor limiting their use in studies of regenerative medicine. Induced pluripotent stem cells (iPSC) are emerging as a novel candidate that could provide an unlimited source of NCC. In the present study, we examined the potential of neural crest tissue-derived periodontal ligament (PDL) iPSC to differentiate into neural crest-like cells (NCLC) relative to iPSC generated from a non-neural crest derived tissue, foreskin fibroblasts (FF). We detected high HNK1 expression during the differentiation of PDL and FF iPSC into NCLC as a marker for enriching for a population of cells with NCC characteristics. We isolated PDL iPSC- and FF iPSC-derived NCLC, which highly expressed HNK1. A high proportion of the HNK1-positive cell populations generated, expressed the MSC markers, whilst very few cells expressed the pluripotency markers or the hematopoietic markers. The PDL and FF HNK1-positive populations gave rise to smooth muscle, neural, glial, osteoblastic and adipocytic like cells and exhibited higher expression of smooth muscle, neural, and glial cell-associated markers than the PDL and FF HNK1-negative populations. Interestingly, the HNK1-positive cells derived from the PDL-iPSC exhibited a greater ability to differentiate into smooth muscle, neural, glial cells and adipocytes, than the HNK1-positive cells derived from the FF-iPSC. Our work suggests that HNK1-enriched NCLC from neural crest tissue-derived iPSC more closely resemble the phenotypic and functional hallmarks of NCC compared to the HNK1-low population and non-neural crest iPSC-derived NCLC. J. Cell. Physiol. 232: 402-416, 2017. 2016 Wiley Periodicals, Inc.

2016 Wiley Periodicals, Inc.

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Generation of Neural Crest-Like Cells From Human ...

Platelet-rich plasma: intra-articular knee injections …

Platelet-rich plasma (PRP) is a natural concentrate of autologous blood growth factors experimented in different fields of medicine in order to test its potential to enhance tissue regeneration. The aim of our study is to explore this novel approach to treat degenerative lesions of articular cartilage of the knee. One hundred consecutive patients, affected by chronic degenerative condition of the knee, were treated with PRP intra-articular injections (115 knees treated). The procedure consisted of 150-ml of venous blood collected and twice centrifugated: 3 PRP units of 5 ml each were used for the injections. Patients were clinically prospectively evaluated before and at the end of the treatment, and at 6 and 12 months follow-up. IKDC, objective and subjective, and EQ VAS were used for clinical evaluation. Statistical analysis was performed to evaluate the significance of sex, age, grade of OA and BMI. A statistically significant improvement of all clinical scores was obtained from the basal evaluation to the end of the therapy and at 6-12 months follow-up (P < 0.0005). The results remained stable from the end of the therapy to 6 months follow up, whereas they became significantly worse at 12 months follow up (P = 0.02), even if still significantly higher respect to the basal level (P < 0.0005). The preliminary results indicate that the treatment with PRP injections is safe and has the potential to reduce pain and improve knee function and quality of live in younger patients with low degree of articular degeneration.

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Platelet-rich plasma: intra-articular knee injections ...