Cells Weekly – April 24, 2016

by Alexey Bersenev on April 24, 2016 · 0 comments

in notes

Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!

BRTI

1. Islets transplantation in diabetes is on a way to standard of care
Human pancreatic islets transplantation in type 1 diabetes has been experimental procedure in the number of highly specialized medical centers for about two decades, but had not became a standard of care. Based on reported data, the benefit is significant, however there is a lack of large multicenter studies. This week results of Phase 3 multicenter clinical trial, assessing long-term efficacy of islet transplantation, were published in Diabetes Care. The same clinical/ manufacturing protocol was applied by 8 centers and results were reproducible. The study met primary end points, demonstrating glycemic control, freedom of severe hypoglycemic events and insulin-independence.

The primary end point was successfully met by 87.5% of subjects at 1 year, and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years.

At one year time point, 52% of patients were insulin-independent. This study will serve as a bridge to licensing technology and FDA approval. It is interesting to see who is going to be BLA holder and how technology will be adopted as new standard of care.

2. Hematopoietic stem cell regulator impacts lifespan of mice
A group of researchers from Germany described a new gene-regulator of hematopoiesis in aging, called Per2.

Here, we conducted an in vivo RNA-mediated interference (RNAi) screen targeting 459 putative tumour suppressor genes to identify hitherto uncharacterized checkpoint responses limiting the self-renewal and functional reserve of HSCs in response to DNA damage. The current study provides experimental evidence that the upregulation of Per2 contributes to the induction of DNA damage responses in haematopoietic stem and progenitor cells and to the selective vulnerability of Ly-biased HSCs to DNA damage and ageing.

Deletion of Per2 ameliorates DNA damage with age, improves lymphopoisis and “normalizes” immune function in aged mice. As a consequence of such “immune system improvements”, lifespan of Per2 knockout mice was significantly extended, compared to wild type mice.

3. Progress in cell-gene therapy of SCID
Results of the clinical gene therapy study for X-linked severe combined immunodeficiency (SCID-X1), were published this week in Science TM. Unlike previous gene therapy studies of SCID, this one included “older patients” (10-26 yo), who failed hematopoeitic stem cell transplantation as infants:

Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up.

Small study, needs confirmation with bigger number of patients, but preliminary results are very good.

4. Research on CRISPR-edited human embryos is going mainstream
Nature magazine posted a very interesting article about research, involved CRISPR-based genome editing of human embryos. Karolinska Institute in Sweden, among other institutions in China and UK, where experiments with CRISPR-edited human embryos are officially permitted.

A year of discussion about the ethics of embryo-editing research, and perhaps simply the passage of time, seems to have blunted its controversial edge — although such work remains subject to the same ethical anxieties that surround other reproductive-biology experiments. “At least in the scientific community, I sense more support for basic-research applications,” says Lanner, who gained approval for his experiments last June.

“I don’t think there is anything wrong with what these scientists have done,” says Sarah Chan, a bioethicist at the University of Edinburgh, UK. “This work isn’t seeking to do what is still ethically in question. It’s not seeking to create genetically modified human beings.”

5. Cell Therapy Manufacturing and Gene Therapy Congress conference report
Fabio D’Agostino from Newcastle University wrote two reports from the recent Informa’s Cell Therapy Manufacturing and Gene Therapy Congress, which took place about two months ago in Brussels:
The State of the Industry: Cell Therapy Manufacturing and Gene Therapy Post-Conference Report
Next Gen CAR-T Cells & Manufacturing Strategies

One interesting excerpt about CAR T-cell products manufacturing:

Lothar Germeroth explained how Juno have circumvented the need for these approaches with their proprietary Streptamer™ reversible reagents.
The process is no longer based on magnetic beads but on affinity –specific tags (Strep-tags) which are added to CAR proteins of engineered T cells and bind to StrepTactin-coated beads. Strep-tags can then be removed by addition of D-biotin which has even higher affinity for StrepTactin. This reduces the risk of compromising the biological function of the cells and potentially adverse effects of the markers in clinical applications…

6. Microfluidics to improve reprogramming efficiency
Researchers from Italy, used microfluidic device for reprogramming of human fibroblasts into iPS cells:

We report that the efficiency of reprogramming human somatic cells to induced pluripotent stem cells (hiPSCs) can be dramatically improved in a microfluidic environment. Microliter-volume confinement resulted in a 50-fold increase in efficiency over traditional reprogramming by delivery of synthetic mRNAs encoding transcription factors.

Very simple – if you want to boost your reprogramming efficiency 50-fold or so, just downscale everything to microliter volumes!

7. Fetal tissues procurement business
The Daily Signal reports on investigation of pricing and business model in fetal tissues procurement for research. The article is highly politicized, but has nice infographics and refers to official “House investigation”.

According to Republicans involved in the investigation, a researcher paid a middleman procurement company $3,340 for a fetal brain, $595 for a “baby skull matched to upper and lower limbs,” and $890 for “upper and lower limbs with hands and feet.”
Middleman procurement businesses are companies that obtain tissue and other body parts from aborted babies and provide them to institutions or other organizations for research. Under federal law, the transportation of fetal tissue is based on a nonprofit model.

8. New methods and protocols:
Micro-Heart Muscle arrays for toxicity testing and drugs R&D (Sci Rep)
Humanizing NSG mice using busulfan and retro-orbital injection of cord blood-derived CD34+ cells (Blood Res)
A digital PCR-based method for efficient screening of genome edited cells (PLoS ONE)
Optogenetic control of human neurons in organotypic brain cultures (Sci Rep)
Label-retaining kidney cells regenerate injured kidney medullary tubules (Stem Cell Rep)
Functional imaging for regenerative medicine (Stem Cell Res Ther)
Isolation and comparative analysis of stem/progenitor cells from different regions of human umbilical cord (Stem Cell Res)

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Clinical Cell Processing News is a series about new protocols, products and techniques for clinical-grade cell processing and manufacturing. Cell processing devices, cultureware, bioreactors, GMP-grade reagents, cell separation techniques. This series is posted every 2 months.

FEATURED:
Review: Toward a scalable and consistent manufacturing process for the production of human MSCs (Cell Gene Ther Insights) FREE

Validation of low-molecular-weight carbohydrate Pentaisomaltose as DMSO replacement for cryoprpeservation of HPC-A products (Transfusion) FREE

Our findings demonstrate that PIM cryopreservation of HPC(A) products provides recovery of CD34+ cells, CD34+ subpopulations, and CFCs similar to that of DMSO cryopreservation and therefore may have the potential to be used for cryopreservation of peripheral blood stem cells.

Scalability and process transfer of MSC production from monolayer to microcarrier culture (Cytotherapy) FREE

This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.

1. Clinical manufacturing of umbilical cord MSC on microcarriers (Stem Cell Int) FREE

… a microcarrier selection out of five microcarrier types was made to achieve a suitable growth surface for the cells. The growth characteristics and metabolite consumption and production were used to compare the cells growth in 12-well plate and spinner flask. The goal to determine relevant process parameters to transfer the expansion process into a stirred tank bioreactor was achieved.

2. Validation of CliniMACS Prodigy for CD34+ cell selection (J Transl Med) FREE

As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 “normal scale” selection process on CliniMACS Plus, applicable for 600 × 106 target cells out of 60 × 109 total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed.

3. Validation of pulse-activated plasmonic nanobubbles for processing of heterogenoeus human cell grafts (Mol Ther – Methods) FREE

We employ cell-specific on-demand mechanical intracellular impact from laser pulse-activated plasmonic nanobubbles (PNB) to process heterogeneous human cell grafts ex vivo with dual simultaneous functionality, the high cell type specificity, efficacy and processing rate for transfection of target CD3+ cells and elimination of subsets of unwanted CD25+ cells.

4. Optimization of umbilical cord MSC culture for GMP manufacturing (Stem Cell Int) FREE

UC-MSCs were expanded in medium enriched with 2%, 5%, or 10% pooled human platelet lysate (HPL) eliminating the xenogeneic serum components. When the HPL concentrations were compared, media supplemented with 10% HPL had the highest growth rate, smallest cells, and the most viable cells at passage. UC-MSCs grown in 10% HPL had surface marker expression typical of MSCs, high colony forming efficiency, and could undergo trilineage differentiation. The new protocol standardizes manufacturing of UC-MSCs and enables clinical translation.

5. Validation of rapid ALDH-based cord blood potency assay (Blood)

… we have developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDHbr) along with viable CD45+, CD34+ cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with pre-specified criteria testing Accuracy, Specificity, Repeatability, Intermediate Precision, and Linearity.

6. Validation of platelet lysate for expansion of MSC derived from patients with critical limb ischemia (J Vasc Surg)

PL promotes the rapid expansion of MSCs from CLI and healthy persons. Importantly, MSCs expanded from CLI patients demonstrate the desired angiogenic activity compared with their healthy counterparts. We conclude that autologous MSCs from CLI patients can be sufficiently expanded with PL and be expected to deliver requisite angiogenic effects in vivo.

7. Optimization and modeling of MSC production om microcarrier in stirred bioreactors (Stem Cell Int) FREE

Our established multiregression model makes the rapid definition of the suspension criteria for different working volumes possible and supports the optimization of microcarrier-based, wave-mixed bioreactors used for hASC cultivations. The consideration of further microcarrier types in the regression model would even allow hMSC expansions other than hASCs.

8. DMSO-free cryopreservation of Wharton’s jelly-derived MSC (J Cell Biochem)

In this study, we compared the effect of two different cryoprotectants (DMSO & cocktail solution) on post-thaw cell behavior upon freezing of WJ tissue following two different freezing protocols [Conventional (-1°C/min) & programmed]. The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO.”>In this study, we compared the effect of two different cryoprotectants (DMSO & cocktail solution) on post-thaw cell behavior upon freezing of WJ tissue following two different freezing protocols [Conventional (-1°C/min) & programmed]. The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO.

9. Validation of hypothermic storage of human pluripotent stem cell-derived cardiomyocytes (Stem Cells TM) FREE

… it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs.

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Cells Weekly – April 17, 2016

by Alexey Bersenev on April 18, 2016 · 0 comments

in notes

Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!

BRTI

1. Therapeutic use of iPS cells from older people could be problematic
Research team led by Shoukhrat Mitalipov, have published a study this week, where showed that iPS cells accumulate mutations of mitochondrial DNA with donor’s age. It could negatively affect function of iPS cells and their progeny. From Nature News:

… the researchers analysed skin and blood samples from 14 people aged between 24 and 72. The older the person was, the more mutations his or her mitochondria acquired. A few of the mutations occurred in DNA that coded for proteins — which might affect how well the iPS cells would function if transplanted into a patient.

Mitalipov suggests that researchers who want to use iPS cells in treatments should isolate at least ten cells, and then use the one with the best mitochondria to create a cell line.

Dieter Egli, a regenerative-medicine researcher at the New York Stem Cell Foundation, says that the findings provide an argument for using embryonic stem cells instead of iPS cells. “This is definitely going to have an impact” on iPS trials, he says. Screening cell lines is especially important if researchers are to use them in the clinic rather than just in the lab.

2. Patent battles can poison academic collaboration
Jacob Sherkow – a Professor of Law at New York Law School wrote a great piece in Nature this week – CRISPR: Pursuit of profit poisons collaboration. I’d highly recommend to read it!

I am concerned that such involvement in commercialization has the potential to clash with the broader, educational mission of research institutions.
Universities worldwide have long strived to foster a culture of scientific collaboration. Even when universities have obtained broad patents, as the Carnegie Institute of Washington in Washington DC did in the early 2000s for a gene-expression control technology known as RNA interference, licences have been cheap and easy for researchers to obtain…

But an obvious danger of increasing the focus on commercialization is that educational institutions will view scientific research as a path to profit, above all else. It is not hard to imagine that patent disputes might lead to university administrators pushing certain views on their scientists, denigrating collaboration with researchers from competing institutions and tasking tenure committees with valuing patents over publications.

I’m also deeply concerned… Now, replace “CRISPR” to “CART” in the title of Sherkow’s article…

3. Cell therapy clinical trials for autoimmune diseases
Parent’s Guide to Cord Blood Foundation posted 5-years trend analysis of clinical trials databases listings in cell therapy for autoimmune diseases. I especially like the graph which breaks down cell types:

4. Efficacy of cardiac cell therapy is diminished in patients with diabetes
Very interesting results of cardiac cell therapy trial were published in Stem Cells TM. Autologous mobilized CD34+ cells were therapeutically used in patients with dilated cardiomyopathy. Experimental therapy was useless in subgroup of patients with diabetes:

These results demonstrate that patients with dilated cardiomyopathy and diabetes do not benefit from autologous CD34+ cell therapy. This finding could serve as a useful tool when selecting heart failure patients for future clinical studies in the field of stem cell therapy.

5. Gene therapy of ADA-SCID is near approval in Europe
About 2 weeks ago, European agency EMA recommended for approval Strimvelis – gene therapy product for one type of severe combined immunodeficiency syndrome, commercialized by GSK. Geneticist and blogger Ricki Lewis wrote a great post on DNA Science Blog about the history, background information of ADA-SCID and differences between gene therapy and gene editing:

I wonder how many people realize, especially those fearful of how gene editing might be misused, that the gene therapy that is nearing approval actually entered clinical trials 26 years ago?
Yes, more than two decades to approve a gene therapy.

6. In utero stem cell therapy is entering a clinical trial
Fascinating story about in utero stem cell therapy of osteogenesis imperfecta was posted this week by Science news. The article brings up a personal story of Oliver Semler, who has the same condition:

He attended medical school and became a pediatrician at the University of Cologne in Germany, where he cares for about 250 children with his condition. Semler is now preparing for a first in OI and well beyond: a clinical trial of a stem cell treatment for afflicted fetuses, which aims to give them a healthier start to life than he had himself.

The story describes history of the first case of in utero stem cell transplantation, performed in 2002 and, also shares some details of new proposed trial:

An OI trial, called BOOSTB4, is now edging toward the starting line. Götherström, David, Semler, and others have secured more than $9 million from the European Union and Swedish Research Council, and are crafting their protocol. Starting later this year, they hope to begin recruiting 15 families across Europe with fetuses shown by ultrasound and DNA testing to have severe OI and in the second or third trimester infuse them with MSCs from fetal liver cells…

Highly recommended!

7. New methods and protocols:
Method for intra-bone transplantation of human cord blood CD34+ cells in NSG mice (Sce Rep)
Isolation of bone marrow from murine hind limb long bones (JoVE)
A programmable synthetic lineage-control network for differentiation of iPS cells into insulin-secreting cells (Nat Commun)
MSC seeding on porcine extracellular matrix for cardiovascular applications (PLoS ONE)

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The graph below illustrates the problem of donor organ shortage for transplantation in USA:


In the last two decades, scientists offered a few potential solutions to this problem: (1) whole organ bioengineering (WOBE) via decellularization – recellularization (decell-recell), (2) xenotransplantation and (3) generation of exogenic human organs in animal chimeras. Since introduction of CRISPR-based genome editing, interest to xenotransplantaion is getting hotter right now. Experiments with human-animal chimeras for generation of human organs got into ethical controversy and were depleted of governmental funding support. I think, as of today, the WOBE via recell-decell technology is the most realistic and quick way for moving into the clinic. In this post I’ll focus on some challenges in clinical translation of WOBE products for solid organs replacement. I gathered information mostly from talks and publications from Harald Ott, Doris Taylor, Angela Panoskaltsis-Mortari and Steven Badylak labs.

1. The best source for organs to decell
Whole donor organ is a source of extracellular matrix (ECM) for recell. Human deceased donors seem like the most appropriate source of organs for clinical use of WOBE products. However, there are three major problems with organs from cadavers: (1) availability, (2) quality/ suitability of ECM and (3) variability from product-to-product. Human organs will be used for WOBE product only if they are not suitable for conventional organ transplant and discarded. Due to scarcity of donors, organs as ECM source for WOBE will be rarely available. If you finally got an organ for decell procedure, it will be “low quality”. ECM from diseased/ old donors is not good and could negatively affect decell-recell procedure. Harald Ott wrote in his review:

… mechanical properties of ECM scaffolds derived from fibrotic lungs were different from healthy donor tissue, and elicited a profibrotic response in fibroblasts [6]. In discarded donor hearts, we found that atherosclerotic and structural heart disease lead to permanent alterations of the ECM scaffold, and therefore persist through the process of decellularization.

Potential solution: Organs from humanized pigs! You can set a manufacturing plant, where production of humanized pig organ ECMs will be standardized and scaled up. Progress in humanization  via gene-modification techniques (for example, described here), makes this alternative very attractive.

2. Generation of consistent product
Due to human donor-to-donor variability (different ECM quality), it is almost impossible to manufacture consistent WOBE product. This is a big obstacle in transition to clinical trials and commercialization. Product must be consistent!
Potential solutions:
(a) Automation of decell-recell process. Automation will be required in clinical WOBE product manufacturing. One of recently described automated devices allowed to cut lung decell process from 1 week to 1 day, making ECMs more consistent. Essentially device made of tubing sets, connecting perfusion buffers with organ vasculature through valves system. The software for this device is available as open code for academics. Automation is the only way to scale up the manufacturing and bring cost of the WOBE product down.
(b) Using clean pig facilities for the first step of processing (organ harvest and decell) will enable scaled manufacturing of high quality whole organ ECMs.

3. Availability of tools and clinical-grade bioreactors
You may see variety of bioreactors for organ bioengineering (see here, here and here) from research labs. All of them are custom made, sometimes in-house. As of now, tools manufacturers are not in hurry to make clinical-grade systems for donor organ perfusion and bioreactors for WOBE products culture. Perhaps, they don’t see market opportunity here yet and refrain to invest.
Potential solutions: Implement clinical systems for organ perfusion, such as TransMedics and OrganOx. Manufacturers of organ bioreactors for research should make clinical closed systems available. Perfusion solutions manufacturers have to make them clinical-grade.

4. Manufacturing release criteria of decell organ scaffold
In the future, perfusion-decell and recell steps of manufacturing could be done in different facilities. In case of centralized mass manufacturing of decell scaffolds, strict release criteria and certificate of analysis should be developed. The single most important specific criteria is efficiency of decell, measured by residual DNA/ cell content. An example of such criteria you can find in Badylak’s review:

Three relatively stringent criteria have been proposed to establish sufficient decellularization: specifically, the remaining ECM scaffold must have 1) less than 50 ng of dsDNA per mg of dry weight, 2) DNA fragments less than 200 bp in length, and 3) no visible nuclear material in histologic analysis with DAPI or H&E

If you’re using humanized pig organs, you have to test residual pig cells/ DNA, which can cause strong immune response. Unfortunately, there are not many antibodies and reagents available to ID pig cells. The next important test to include is assessment of integrity/ mechanical properties of scaffold (for example, collagen, elastin, GAG content – reviewed here). Of course, decell scaffold must be sterile. Pig-derived scaffold also must be tested for endogenous porcine viruses (for example, PERV detection test). Detection systems for porcine viruses must be commercially available and approved for biologic product release testing.

5. Thrombogenicity of decellularized ECM
The biggest short-term problem after WOBE product implantation is thrombosis. Decade of research have demonstrated that denuded vasculature of organ scaffold is highly highly thromobogenic.
Potential solution: No-brainer here – if you want your engineered organ work properly in vivo, you must re-endothelialize it! Anti-coagulants are useless in this situation. Endothelium seeding must be stable and cover whole vascular system.

6. The best strategy to recell
Recellularization itself is bringing a number of challenges. What is the best cell source for recell? What is the best strategy to do it? How to ensure cell retention? How many cells is enough? There are no easy universal solutions here, but there is a lot of research studies, specific to each organ.
(a) Cell types. Due to low proliferative and differentiation capacity, primary cells is not good source for recell. Progenitor and stem cells, including iPS are currently studied as source for recell. However, the use of autologous iPS-based recell, is not as easy as many people claim.
(b) Strategy. Re-endothelialization could be the most clinically important part of recell. Some researchers recommend re-endothelialization as the first step. The second step is to make WOBE product stroma. Mesenchymal stromal cells is the most widely used source for stroma re-creation in decell scaffold. Finally, the last step is using progenitor/ stem cells for expansion and differentiation to highly specialized organ-specific cell types. For example, auto- iPS cell-derived endoderm progenitors for the lung. Ideally, expansion and differentiation of stem/ progenitor cells is completed in situ.
(c) Cell retention. Good cell retention within WOBE product is a big problem. An example from Ott’s review:

Vascular perfusion as a different seeding approach was used when decellularized mice hearts were repopulated with human iPSC-derived cardiac progenitor cells…
This utilized the ability of progenitor cells to spontaneously migrate from the vascular bed to the ECM. After terminal cell differentiation in situ, cardiomyocytes were found in the ventricular wall and ventricular septum. However, 85–90% of cells were washed out from the vascular conduit within the first 7 days.

In his recent study, only about 5% of recellularized lung was covered by iPS cell-derived endothelium after few days in culture.
(d) Cell number. One may think that in recell the more cells the better. Yes, solid organs made of many many billions of cells. For example, human heart will require ~4 billions cardiomyocytes for complete recell (as of today, max # of recell cardiomyocytes = 0.5 billions for human heart was achieved by Ott’s group). However, after full re-endothelialization, significant part of organ maturation and remodeling could be completed in vivo.  Few researchers now bet on the concept of recell organ as “inductive template”, which will be remodeled by endogenous cells and fully matured in vivo.
(e) Seeding. There are many cell seeding techniques described, but seem like combination of vascular perfusion of cell suspension with direct intra-parenchymal injections will work the best.

7. Immunogenicity
The host immune response to decellularized and recell ECM remains understudied. Implantation of commercially available decell ECM causes profound immune response with shift from pro-inflammatory M1- to tissue remodeling M2 macrophages with degree of decell. It is important to recognize the difference between host immune rejection response and “tissue remodeling” response:

With removal of cells, native ECM scaffolds are depleted from major histocompatibility complex class I and II antigens and therefore would not elicit cell-mediated graft rejection. However, retained cell debris can result in a host-induced inflammatory cascade.
… an M2 macrophage-mediated immune response toward acellular matrix may have positive effects on in-vivo ECM remodeling.

In the recent study, Ott’s group compared macrophage infiltration of human cadaveric heart tissue, human decell heart ECM and porcine decell heart ECM in rat host. Overall, infiltration of CD163+ macrophage was profound without significant difference between 3 types of scaffolds. The humoral immune response, which could be disastrous for implanted WOBE product, will totally depend on efficiency of decell (quality of ECM) and nature of recell components (allo- cells, culture in xeno+ conditions). Immunnosupression may be required, analogously to organ transplant.

8. Regulation
Decell ECMs are currently approved on a market as devices and used for regeneration of soft tissues. However, there is no regulatory framework for WOBE product. Theoretically, it could be regulated as combination product by FDA CDRH (device) and CBER (cells/ tissues) centers. Seem like the most practical approach is to split manufacturing and regulation for 2 parts: manufacturer #1 makes decell organ ECM (device) and sells it to manufacturer #2, who does recell part (tissue/ cell drug) and send it to transplant center.

Overall, still a lot of work should be done before the first clinical trials of WOBE products. My best estimation will be 2-5 years from now. Obviously, decell-recell tissue patches, sheets, hollow organs and parts of solid organs (liver or lung lobe) will be ahead of whole solid organs, but we will get there!

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Cells Weekly – April 10, 2016

by Alexey Bersenev April 11, 2016 notes

Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night! 1. The second report on CRISPR-based gene editing of human embryos This week, researchers from China published a study, where CRISPR-based gene editing was used to make […]

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Stem cell hype in clinical tissue engineering of hollow organs

by Alexey Bersenev April 10, 2016 tissue engineering

As you may know, the scandal around “tissue engineering pioneer” Paolo Macchiarini is unfolding and getting uglier (read here and here). To be honest, since 2008 I was really thrilled by initial results of the first trachea transplants and by Macchiarini’s confidence. What I did not like since the beginning was “stem cell branding”. Macchiarini’s […]

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Cellular therapy brings attention to cytometry

by Alexey Bersenev April 5, 2016 cytometry

This is a guest post by Ruud Hulspas, Ph.D. Industry has a different approach to Research & Development than academia. While the academic approach typically focuses on discovery, innovation and proof-of-principle, industry adds feasibility and product (manufacturing) requirements early on to the timelines of R&D projects. Consequently, the tools, technologies, reagents and expertise chosen for […]

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Cells Weekly – April 3, 2016

by Alexey Bersenev April 4, 2016 notes

Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night! 1. Open software to reprogram cells It was published in Science on April 1st and it was not a joke! Researchers from MIT created a software to […]

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Update on GDF11 controversy

by Alexey Bersenev April 3, 2016 reproducibility

The controversy around “anti-aging circulating factor” GDF11 continue to unfold. Just to remind you, “high profile” study by Harvard’s Amy Wagers group, described GDF11 as “rejuvenating circulating factor”, which reversed functional impairment of aged muscle stem cells. Another study, performed in collaboration with Wager’s lab, demonstrated that increase of GDF11 level led to reversal of […]

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Impact of starting material T-cell composition on outcome of CAR T-cell therapy

by Alexey Bersenev April 1, 2016 cell product

As I was discussed before, apheresis product is the most variable raw material in CAR T-cell manufacturing. Cellular composition of this starting material is highly heterogeneous between patients, therefore, manufacturing of consistent CAR T-cell product is a big challenge. One of the most interesting questions in the field – Can T-cell composition of starting material […]

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