Stem Cell Clinic

Stem Cell Transplants Used to Grow Fully Functional Lungs in Mice – Technology Networks

Researchers at Columbia University were able to grow fully functional lungs in mouse embryos using transplanted stem cells. The findings suggest that it may be ultimately possible to use the technique to grow human lungs in animals for patients who need transplants and to study new lung treatments.

Millions of people worldwide who suffer from incurable lung diseases die without treatment due to the limited supply of donor lungs for transplantation, said co-senior author Wellington V. Cardoso, MD, PhD, professor of medicine and of genetics & development at Columbia University Vagelos College of Physicians and Surgeons. Our study shows that it may eventually be possible to develop new strategies for generating human lungs in animals for transplantation as an alternative to waiting for donor lungs.

Researchers have dedicated major efforts to bioengineer lungs by growing stem cells on synthetic scaffolds or in lungs that have been stripped of their original cells. Though substantial progress has been made, researchers have been unable to generate a fully functional lung capable of maintaining survival in animal models.

We thought it might be simpler to grow new lungs in a developing animal, so that we could take advantage of the animals natural signals for lung development, says first author Munemasa Mori, MD, PhD, instructor of medicine at Columbia University Vagelos College of Physicians and Surgeons.

The researchers first challenge was to create tissue culture conditions that would allow the donor stem cells to expand proliferate and maintain their ability to transform into many different cell types.

Next, the researchers implanted these stem cells in two types of engineered mouse embryos. One type lacked the stem cells that develop into mature lung cells and another could not produce enough of the cells to make a lung. This procedure created a chimeric embryo that was a mix of donor and host cells.

The implanted stem cells outcompeted the host cells for growth-promoting molecules present in the embryo, leading to the formation of functional lungs that allowed the mice to live well into adulthood. A variety of lung function tests confirmed that the chimeric lungs worked as well as normal mouse lungs, with no signs of rejection.

The stem cells were implanted before the embryos immunological system was turned on, which may explain why the organs were not rejected, says Mori, who will later test his approach in larger animals and in interspecies organ transplants.

Many of the signals for lung development are conserved across species, from frogs to mice to humans, so the idea of using animals to grow human lungs is not out of the question, Cardoso says.

The research was performed in collaboration with Hiromitsu Nakauchi, PhD, a professor at Stanford University School of Medicine and the University of Tokyo, a co-senior author of the paper.

Reference:Mori, M., Furuhashi, K., Danielsson, J. A., Hirata, Y., Kakiuchi, M., Lin, C.-S., Cardoso, W. V. (2019). Generation of functional lungs via conditional blastocyst complementation using pluripotent stem cells. Nature Medicine. https://doi.org/10.1038/s41591-019-0635-8

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Kadimastem to Present Interim Results of Cohort A of Its Phase 1/2a Clinical Trial in ALS at the 7th International Stem Cell Meeting, in Tel-Aviv,…

NESS ZIONA, Israel, Nov. 11, 2019 /PRNewswire/ --Kadimastem Ltd.(TASE: KDST),a clinical stage cell therapy company, today announced that it will present the interim results of Cohort A of its ongoing Phase 1/2a Clinical Trial in ALS (as published in Company's press release) at the 7th International Stem Cell Meeting, to be held on November 12-13 at the Dan Panorama Hotel in Tel Aviv, Israel.

The International Stem Cell Meeting, hosted by the Israel Stem Cell Society, is a highly reputed conference, participated by international world leaders in stem cell research.

Presentation Details:

Title: "FIRST IN HUMAN CLINICAL TRIALS WITH HUMAN ASTROCYTES AS A NOVEL CELL THERAPY FOR THE TREATMENT OF ALS"

Session:ONGOING CLINICAL TRIALS WITH CELL THERAPY

Presenter:Arik Hasson, PhD, Executive VP, Research and Development, Kadimastem

Date:Wednesday, November 13, 2019

Time:1:50 pm Israel

Location: Dan Panorama Hotel, Tel Aviv, Israel

Rami Epstein, CEO of Kadimastem, stated: "We are pleased to share these results with global leaders in the cell therapy and stem cells industry,demonstrating the potential of AstroRx, our astrocyte-based cell therapy product,to bring treatment to ALS patients, and possibly other neurodegenerative diseases. We look forward to further share data of this ongoing trial, with final results of cohort A expected by year-end 2019and results of cohort B expected in Q3, 2020."

About the Phase 1/2a ALS Clinical Trial

The Phase 1/2a trial is an open label, dose escalating clinical study to evaluate the safety, tolerability and preliminary efficacy of AstroRxcells in patients with ALS. The trial is expected to include 21 patients and is being conducted at the Hadassah Medical Center, Jerusalem, Israel. The primary endpoints of the trial are safety evaluation and tolerability of a single administration of allogeneic astrocytes derived from human Embryonic Stem Cells (hESC), administered in escalating low, medium and high doses (100x106, 250x106, and 500x106 cells, respectively). The medium dose will also be administered in 2 consecutive injections separated by an interval of ~60 days. Secondary end points include efficacy evaluation and measurements. Treatment is administered in addition to the appropriate standard-of-care.

About AstroRx

AstroRx is a clinical grade cell therapy product developed and manufactured by Kadimastem in its GMP-compliant facility, containing functional healthy astrocytes (nervous system support cells) derived from human Embryonic Stem Cells (hESC) that aim to protect diseased motor neurons through several mechanisms of action. The Company's technology enables the injection of AstroRxcells into the spinal cord fluid of patients suffering from Amyotrophic Lateral Sclerosis (ALS) with the goal of supporting the malfunctioning cells in the brain and spinal cord, in order to slow the progression of the disease and improve patients' quality of life and life expectancy. AstroRxhas been shown to be safe and effective in preclinical studies. AstroRxhas been granted orphan drug designation by the FDA.

About ALS

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease causing disfunction in the upper and lower motor nerves that control muscle function. ALS leads to muscle weakness, loss of motor function, paralysis, breathing problems, and eventually death. The average life expectancy of ALS patients is 2-5 years. According to the ALS Therapy Development Institute, it is estimated that there are approximately 450,000 ALS patients worldwide of which 30,000 reside in the US. According to the ALS Foundation for Life, the annual average healthcare costs of an ALS patient in the US are estimated at US$ 200,000. Thus, the annual healthcare costs of ALS patients in the US alone amount to US$ 6 Billion.

About Kadimastem

Kadimastem is a clinical stage cell therapy company, developing and manufacturing "off-the-shelf" allogeneic proprietary cell products based on its platform technology for the expansion and differentiation of Human Embryonic Stem Cells (hESCs) into clinical grade functional cells. AstroRx, the Company's lead program, is a clinical-grade astrocyte cell therapy for the treatment of ALS, currently undergoing a Phase 1/2a clinical trial. In addition, preclinical trials are ongoing with the Company's IsletRx pancreatic functional islet cells for the treatment of insulin dependent diabetes. Kadimastem was founded by Prof. Michel Revel, CSO of the Companyand Professor Emeritus of Molecular Genetics at the Weizmann Institute of Science. Prof. Revel received the Israel Prize for the invention and development of Rebif, a multiple sclerosis blockbuster drug sold worldwide. Kadimastem is traded on the Tel Aviv Stock Exchange (TASE: KDST).

Company Contacts:Yossi Nizhar, CFOy.nizhar@kadimastem.com+972-73-797-1613

Investor and Media Contact:Meirav Gomeh-Bauermeirav@bauerg.com+972-54-476-4979

Global Media Contact:Dasy (Hadas) MandelDirector of Business Development, Kadimastemd.mandel@kadimastem.com+972-73-797-1613

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Kadimastem to Present Interim Results of Cohort A of Its Phase 1/2a Clinical Trial in ALS at the 7th International Stem Cell Meeting, in Tel-Aviv,...

Serving those who serve us – The Hub at Johns Hopkins

ByKristin Hanson

This article was originally published on Nov. 8 on giving.jhu.edu

Between 2001 and the beginning of 2018, more than 1,500 U.S. military service members lost limbs in the line of duty. Although technology has improved the prosthetic devices these people can use, a stubborn obstacle remains: the fragility of human skin.

"Skin was never meant to hold this kind of pressure," says Lee Childers, the senior scientist for the Extremity Trauma and Amputation Center of Excellence at Brooke Army Medical Center in San Antonio, Texas.

"Think about it like a blister on your foot. It's painful, but you can still get by," he continues. "In an amputation, it's a blister on your residual limb. You can't use your prosthesis until the blister is completely healed. If it's your leg [that is affected], you can't walk for two or three weeks. Think about how that would impact your life."

What if there were a way to make the skin at an amputation site tougher, like the palm of your hand or the sole of your foot? Luis Garza, an associate professor of dermatology at Johns Hopkins and leader of the Veteran Amputee Skin Regeneration Program, is developing a cell therapy that could enable prosthetics wearers to use their devices longer.

"This is an example of personalized medicine," Garza says. "We're taking each person's own cells, growing them up, and inserting them back in."

Garza's postdoctoral research focused on skin stem cells. In 2009, he and his department chair, Sewon Kang, began having conversations about how that work could help the increasing numbers of veterans coming back from war with amputations. Garza and his team received grants from the U.S. Department of Defense, National Institutes of Health, and Maryland Stem Cell Fund that have moved the program forward in the past decade.

Garza's team spent the summer of 2019 testing "normal" subjectsthose without amputationsto perfect the procedure, including the dose, content, method, and frequency of the injections. During one appointment, members of Garza's team took biopsies of skin from a subject's scalp and sole. The cells went to a lab where they were grown under an FDA-approved protocol and passed through quality control tests.

In a second appointment, subjects completed a questionnaire and underwent baseline measurements of their skin's thickness and strength. Garza's team then injected a site on the subjects' skin with the stem cells grown from their cells in the lab.

Image caption: Luis Garza, associate professor of dermatology at Johns Hopkins, leads the Veteran Amputee Skin Regeneration Program.

"We're hoping that these stem cell populations will engraft in the new skin," Garza says.

The subjects returned to Hopkins several months later to go through the questionnaire and measurements once more, and Garza's team documented changes.

Confident in the results they gleaned from the normal subjects, Garza's team enrolled its first subject with an amputation in August. Moving from the normal population to the amputation-affected population quickly unearthed some aspects of the therapy Garza didn't anticipate.

"When we talked with him, he said 'I don't want to mess with my one remaining footdo you have to take skin from there?' And we said, 'Actually, no, we could do your palm,'" Garza says.

His team then tested the biopsy and growth of palm cells from subjects in the normal population. "We're moving away from having our product informed purely by biology to letting our therapy development be shaped by the user."

Although federal grants have supported much of the program's progress, private philanthropy has played a role, too. Corporations like Northrop Grumman, foundations like the Alliance for Veteran Support, and grateful patients with and without ties to the armed forces have contributed nearly $300,000. Those gifts have enabled the program to persevere through gaps between federal grants.

A man sits at a desk, speaking with another man who sits beside him. A large microscope sits on the desk, and a brightly colored image of a skin biopsy appears on a computer screen.

Private funds will be increasingly important as the project enters its next phase: extension to military medical centers around the country. Garza's team must prove that the safeguards to protect cells on their round-trip voyage from a test site to Hopkins are effective. They also must secure approval by local institutional review boards for clinical studies.

"Soldiers are used to getting orders, but you can't order someone to be part of a [medical] study," Garza says. "There are hard medical ethics questions around how to make this open to them but ensure they don't feel obligated. We've been working on that for a year, and we probably have another six months or so to go."

Childers stands ready for whenever the program's extension is a go. He will lead the study at Brooke Army Medical Center and feels motivated by the prospect of helping many of the veterans he works with every day.

"We do everything we can to serve those who serve us. This can enable people to return to duty and be redeployed if they choose," he says. "This is game-changing technology that will have an impact for our service members, but also others who live with amputation."

That population includes the hundreds of thousands of Americans who've undergone amputations for complications of diabetes, who must use a wheelchair, or who wear ankle or foot orthoses for help with walking, among others.

"Having the ability to transform skin anywhere you want to target on the body will have gigantic implications across the entire spectrum of our society in many ways," Childers says.

There's a lot of work to be done before such benefits reach the public, Garza cautions. With continued support from donors and the military community, though, he's optimistic about the program's future.

"The challenges are pretty big, but I think within five years, it could happen," he says. "That's the hope."

Disclaimer: The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of the Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force and Department of Defense or the U.S. Government.

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Human Heart Cells Transform in Space; Return to Normal on Earth: Study – The Weather Channel

Representational image

Heart cells are altered in space, but return to normal within 10 days on Earth, say researchers who examined cell-level cardiac function and gene expression in human heart cells cultured aboard the International Space Station (ISS) for 5.5 weeks.

Exposure to microgravity altered the expression of thousands of genes, but largely normal patterns of gene expression reappeared within 10 days after returning to Earth, according to the study published in the journal Stem Cell Reports.

"We're surprised about how quickly human heart muscle cells are able to adapt to the environment in which they are placed, including microgravity," said senior study author Joseph C. Wu from Stanford University.

These studies may not only provide insight into cellular mechanisms that could benefit astronaut health during long-duration spaceflight, but also potentially lay the foundation for new insights into improving heart health on Earth.

Past studies have shown that spaceflight induces physiological changes in cardiac function, including reduced heart rate, lowered arterial pressure, and increased cardiac output.

But to date, most cardiovascular microgravity physiology studies have been conducted either in non-human models or at tissue, organ, or systemic levels.

Relatively little is known about the role of microgravity in influencing human cardiac function at the cellular level.

To address this question, the research team studied human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). They generated hiPSC lines from three individuals by reprogramming blood cells, and then differentiated them into heart cells.

Beating heart cells were then sent to the ISS aboard a SpaceX spacecraft as part of a commercial resupply service mission. Simultaneously, ground control heart cells were cultured on Earth for comparison purposes.

Upon return to Earth, space-flown heart cells showed normal structure and morphology. However, they did adapt by modifying their beating pattern and calcium recycling patterns.

In addition, the researchers performed RNA sequencing of heart cells harvested at 4.5 weeks aboard the ISS, and 10 days after returning to Earth.

These results showed that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples.

Most notably, gene pathways related to mitochondrial function were expressed more in space-flown heart cells.

A comparison of the samples revealed that heart cells adopt a unique gene expression pattern during spaceflight, which reverts to one that is similar to ground-side controls upon return to normal gravity, the study noted.

According to Wu, limitations of the study include its short duration and the use of 2D cell culture.

In future studies, the researchers plan to examine the effects of spaceflight and microgravity using more physiologically relevant hiPSC-derived 3D heart tissues with various cell types, including blood vessel cells.

"We also plan to test different treatments on the human heart cells to determine if we can prevent some of the changes the heart cells undergo during spaceflight," Wu said.

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Human Heart Cells Transform in Space; Return to Normal on Earth: Study - The Weather Channel

The Value and Versatility of Clinical Flow Cytometry – Technology Networks

What is flow cytometry and how does it work?Flow cytometry(FCM) is a scientific technique used to measure the physical and biochemical characteristics of cells.1The sample is injected into the flow cytometer instrument, where it is typically focused to flow one cell at a time past light sources and detectors. Tens of thousands of cells can be examined in seconds to determine their morphology, granularity, scattering and transmission of light, or fluorescence of biomarkers, depending on the variation of FCM used.

The first conventional fluorescence-based flow cytometer was developed and commercialized in the late 60s/early 70s in Germany.2 Over the last five decades, FCM has developed rapidly in terms of the number of its applications and the quantity and dimensionality of the data it generates.1,3 Dr. Minh Doan, formerly of the Imaging Platform of the Broad Institute (USA) and now head of Bioimaging Analytics at GlaxoSmithKline in the USA, states, There have been significant advances in all three Vs of flow cytometry data: velocity (throughput/speed of data acquisition), volume (data content), and variety (sample types and signal acquisition technology).

Michael Parsons, manager of the Flow Cytometry Core of the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, agrees. The two biggest trends in flow cytometry are high content data and the merging of technologies from separate disciplines. For example, the last five years or so have seen the emergence of mass cytometry, which merges the disciplines of flow cytometry and mass spectrometry. In its latest iteration, an image cytometry module has been incorporated to generate unprecedented amounts of content (number of measured parameters) from relatively small amounts of patient tissue. Spectral flow cytometry has also established itself as an important emerging technology. Indeed, mass cytometry can now measure up to 50 features on a single cell simultaneously using antibodies tagged with rare earth metals,4 and imaging flow cytometry allows for 1000s of morphological features and multiple fluorescence markers to be analyzed per cell.3Flow cytometry, therefore, has inarguable potential as a clinical tool for disease diagnosis, prognosis, and therapeutic monitoring. However, some challenges remain in translating the full promise of FCM into clinical practice. Here, some of the current clinical applications of FCM will be discussed, as well as some of the compelling new applications being researched.

Similarly, FCM of liquid biopsies could be used to detect circulating tumor cells in the bloodstream.3 These cells are extremely rare, and with its high sensitivity, FCM is perfectly poised to make a significant impact in this area. This approach has potential for the clinical detection of early-stage cancer as well as the detection of circulating metastatic or drug-resistant cancer cells. For example, a study published earlier this year described label-free liquid biopsy with very high throughput (> 1 million cells/second) for drug-susceptibility testing during leukemia treatment.8

Prior to an organ transplant, FCM can be used to crossmatch the patient's serum with donor lymphocytes to detect antibodies that could result in organ rejection.1 Postoperatively, the analysis of various cell markers on the peripheral blood lymphocytes can indicate early transplant rejection, detect bone marrow toxicity arising from immunosuppressive therapies, and help differentiate infections from organ rejection. For blood transfusions, FCM can be used to detect contamination of blood with residual white blood cells, which can have adverse effects such as pulmonary edema.9Groups such as Dr. Roshini Abrahams at Nationwide Childrens Hospital in Ohio, USA, are using FCM to diagnose primary immunodeficiency disorders with the use of immunophenotyping and functional assays.10 These disorders are caused by genetic mutations that result in defects in the immune system, such as X-linked (Brutons) agammaglobulinemia and X-linked hyper-IgM syndrome. Over 300 of these disorders have been identified thus far, and the causative mutations lower immune defense against the attack of infections.

HIV is, of course, an example of a secondary (acquired) immunodeficiency disorder. FCM analysis of CD4 and other markers on lymphocytes in the peripheral blood is used to monitor the treatment of HIV patients, and a CD4 count <200 cells/mL together with a positive antibody test for HIV is used as a diagnostic for AIDS.1 Secondary immunodeficiencies can also be caused by e.g., substance abuse, malnutrition, other medical conditions, and certain medical treatments. FCM of a panel of markers can be used to confirm suspected cases.1In pregnancy, when a Rhesus blood group D-negative mother carries a D-positive fetus, fetal-maternal bleeding can sensitize the mother to the D-positive blood cells from the fetus and this can be fatal to subsequent D-positive newborns.11 FCM is used to measure the degree of fetal-maternal hemorrhage to determine the correct dose of prophylactics to be administered shortly after delivery.

In addition to oncology and immunology applications, FCM is also used to diagnose a variety of rare hematologic disorders12 as well as autoimmune/autoinflammatory disorders such as spondylarthritis (arthritis of the spine).13 Another area of research that is likely to give rise to increasing clinical applications in the future is that of platelet activity, which is important in many clinical conditions.1,14

Experts suggest that it may be possible to overcome this data analysis hurdle by applying machine learning approaches coupled with further standardization of FCM workflows.3,15 The most exciting applications of high content data revolve around the use of machine learning, in particular, deep learning, to extract relevant meaning from large data sets. Machine learning, coupled with big data, has the potential for driving diagnosis and treatment options tailored to the patients disease in a timely manner, says Dr. Parsons. In addition, Prof. Sadao Ota of RCAST at the University of Tokyo, Japan, points out, We still need to figure out how to design a workflow that convincingly validates diagnostic results, especially if the diagnosis employs the power of machine learning. Such developments are necessary before the rich information content of advanced FCM technology can be fully applied in the clinic.

In terms of other future advances in the field, Prof. Ota specifically makes mention of the potential of cell sorters combined with FCM.16 There are exciting and unique applications of sorters in fields such as cell therapy and regenerative medicine. Also, creating key applications of imaging cell sorters in pharmaceutical fields may accelerate global drug discovery. Dr. Doan concurs, Disease heterogeneity makes it hard to validate findings. Perhaps the use of flow cytometry with sorting capability can help such validation, where events-of-interest collected by flow cytometry can be validated with other downstream assays. Finally, as Dr. Doan notes, With multiple layers of data(types) incorporated altogether, there are now possibilities to do more with less, i.e., label-free sample measurement, which could lead to more direct, faster, and smarter diagnoses. Rare events (e.g., metastatic cancer cells) may soon be detected better than before.References1.Bakke A.C. Clinical Applications of Flow Cytometry. Laboratory Medicine. 2000; 31(2): 97104. doi: 10.1309/FC96-DDY4-2CRA-71FK.2.Herzenberg L.A., Parks D., Sahaf B., Perez O., Roederer M., Herzenberg L.A. The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. Clinical Chemistry. 2002;48(10):181918273.Doan M., Vorobjev I., Rees P., Filby A., Wolkenhauer O., Goldfeld A.E., Lieberman J., Barteneva N., Carpenter A.E., Hennig H. Diagnostic potential of imaging flow cytometry. Trends in Biotechnology. 2018;36(7):649652. doi: 10.1016/j.tibtech.2017.12.008.4.Olsen L.R, Leipold M.D., Pedersen C.B., Maecker H.T. The anatomy of single cell mass cytometry data. Cytometry Part A. 2019;95(2):156172. doi: 10.1002/cyto.a.23621.5.Laerum O.D., Farsund T. Clinical application of flow cytometry: a review. Cytometry. 1981;2(1):113. doi: 10.1002/cyto.990020102.6.Li J., Wertheim G., Paessler M., Pillai V. Flow cytometry in pediatric hematopoietic malignancies. Clinics in Laboratory Medicine. 2017;37(4):879893. doi: 10.1016/j.cll.2017.07.009.7.Gupta S., Devidas M., Loh M.L., Raetz E.A., Chen S., Wang C., Brown P., Carroll A.J., Heerema N.A., Gastier-Foster J.M., Dunsmore K.P., Larsen E.C., Maloney K.W., Mattano L.A. Jr., Winter S.S., Winick N.J., Carroll W.L., Hunger S.P., Borowitz M.J., Wood B.L. Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Childrens Oncology Group (COG). Leukemia. 2018;32(6):13701379. doi: 10.1038/s41375-018-0039-7.8.Kobayashi H., Lei C., Wu Y., Huang C-J., Yasumoto A., Jona M., Li W., Wu Y., Yalikun Y., Jiang Y., Guo B., Sun C-W., Tanaka Y., Yamada M., Yatomi Y., Goda K. Intelligent whole-blood imaging flow cytometry for simple, rapid, and cost-effective drug-susceptibility testing of leukemia. Lab on a Chip. 2019;19(16):26882698. doi: 10.1039/c8lc01370e.9.Castegnaro S., Dragone P., Chieregato K., Alghisi A., Rodeghiero F., Astori G. Enumeration of residual white blood cells in leukoreduced blood products: Comparing flow cytometry with a portable microscopic cell counter. Transfusion and Apheresis Science. 2016;54(2):266270. doi: 10.1016/j.transci.2015.10.001.10.Abraham R.S., Aubert G. Flow cytometry, a versatile tool for diagnosis and monitoring of primary immunodeficiencies. Clinical and Vaccine Immunology. 2016;23(4):254271. doi: 10.1128/CVI.00001-16.11.Kim Y.A., Makar R.S. Detection of fetomaternal hemorrhage. American Journal of Hematology. 2012;87(4):417423. doi: 10.1002/ajh.22255.12.Bn M.C., Le Bris Y., Robillard N., Wuillme S., Fouassier M., Eveillard M. Flow cytometry in hematological nonmalignant disorders. International Journal of Laboratory Hematology. 2016;38(1):516. doi: 10.1111/ijlh.12438.13.Duan Z., Gui Y., Li C., Lin J., Gober H.J., Qin J., Li D., Wang L. The immune dysfunction in ankylosing spondylitis patients. Bioscience Trends. 2017;11(1):6976. doi: 10.5582/bst.2016.01171.14.Pasalic L. Assessment of platelet function in whole blood by flow cytometry. Methods in Molecular Biology. 2017;1646:349367. doi: 10.1007/978-1-4939-7196-1_27.15.Doan M., Carpenter A.E. Leveraging machine vision in cell-based diagnostics to do more with less. Nature Materials. 2019;18(5):414418. doi: 10.1038/s41563-019-0339-y.16.Ota S., Horisaki R., Kawamura Y., Ugawa M., Sato I., Hashimoto K., Kamesawa R., Setoyama K., Yamaguchi S., Fujiu K., Waki K., Noji H. Ghost cytometry. Science. 2018;360(6394):12461251. doi: 10.1126/science.aan0096.

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The Value and Versatility of Clinical Flow Cytometry - Technology Networks