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 human embryos resistant to HIV. They alter CCR5 gene with success rate ~ 15%. The embryos, unsuitable for IVF were used. After 3 days, embryos were destroyed. This is a world second report on gene editing of human embryos. Read some interesting opinions in Nature News:
Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, Japan, sees no problem with how the experiments were conducted — a local ethics committee approved them, and the egg donors gave their informed consent — but he questions their necessity. “Introducing CCR5Δ32 and trying repair, even in non-viable embryos, is just playing with human embryos,” Ishii says.
Also read MIT Tech Review:
The scientists cautioned that they believe making actual genetically modified babies should be “strictly prohibited”—but perhaps only until the technology is perfected. “We believe that is necessary to keep developing and improving the technologies for precise genetic modification in humans,” Fan’s team said, since gene modification could “provide solutions for genetic diseases” and improve human health.
2. Long-term survival of humanized pig heart in baboon
Researchers from NIH have demonstrated that humanized pig hearts can function and survive in baboons for 1-2 years under immunosuppression:
Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure.
Keith Horvath’s group has been working on humanization of pig organs for a long time. The combination of the latest gene modification 1-3 galactosyltransferase gene knockout + human complement regulatory protein CD46 + human thrombomodulin (GTKO.hCD46.hTBM) with few immunomodulatory drugs resulted in better outcome. The study bought us one step closer to xenotransplantation trial!
3. Result of cardiac cell therapy trial by Vericel
US-based regenerative medicine company Vericel has released publication with results of their ixCELL-DCM clinical trial. Efficacy of bone marrow-derived autologous cell product Ixmyelocel-T was assessed in patients with ischemic dilated cardiomyopathy. This randomized placebo-controlled study included 126 participants (60 in ixmyelocel-T group and 66 in placebo group). From company’s press release:
“The ixCELL-DCM study met its primary endpoint of demonstrating a reduction in the total number of all-cause deaths, cardiovascular hospitalizations, or unplanned outpatient and emergency department visits to treat acute decompensated heart failure during the 12 months following treatment with ixmyelocel-T compared to placebo,” said Dr. David Recker, Vericel’s chief medical officer. “From a safety perspective, the incidence of adverse events, including serious adverse events, in patients treated with ixmyelocel-T was comparable to or lower than patients in the placebo group. We are very excited about the results of this clinical trial and greatly appreciate the contributions of the patients, investigators and dedicated personnel who participated in this study.”
It is important to note here that secondary efficacy end points of the study were not met (no difference with placebo). Despite company’s excitement, investors were not impressed by trial results and dump the stock on a day of release.
4. Tracking of somatic cell mutational history during reprogramming
Very interesting study was published this week in PLoS Genetics. The authors analyzed mutational history of somatic cell by using monoclonal line of endothelial progenitor cells, reprogrammed to iPS cells:
We find that reprogramming is mutagenic at the nucleotide level and, similar to previous reports [20,21], not at the chromosomal level. The nucleotide-level mutations are associated with a sharp increase in the proportion of mutations associated with oxidative DNA damage. However established iPSCs seem to be substantially protected from DNA damage by their pluripotent state.
Over the relatively few generations we studied, we could not find any evidence of a selection sweep within the culture. Notably we did not find any driver mutations in our analyses.
The first author said:
“None of the mutations we found in induced pluripotent stem cells were cancer-driver mutations or mutations in cancer-causing genes. We didn’t find anything that would preclude the use of iPS cells in therapeutic medicine.”
5. Hematopoietic stem cell transplantation to treat Myasthenia Gravis
Very good results of experimental treatment of Myasthenia Gravis (MG) were reported by Canadian researchers in JAMA Neurology. The study involved transplantation of mobilized autologous hematopoietic stem cells and included only 7 patients:
All patients achieved durable MGFA complete stable remission with no residual MG symptoms and freedom from any ongoing MG therapy (MGFA postintervention status of complete stable remission).
If results could be reproduced in larger trials, MG could become a new indication where hematopoietic stem cell transplant can lead to long-term remission.
6. Bioprinting of neural tissue
Australian researchers developed a method for bioprinting of human neural stem cells:
Here, a first example of constructing neural tissue by printing human neural stem cells that are differentiated in situ to functional neurons and supporting neuroglia is reported. The supporting biomaterial incorporates a novel clinically relevant polysaccharide-based bioink comprising alginate, carboxymethyl-chitosan, and agarose. The printed bioink rapidly gels by stable cross-linking to form a porous 3D scaffold encapsulating stem cells for in situ expansion and differentiation.
The next step will be to test bioprinted tissue in transplantation models.
7. Investment of US Government in regenerative medicine
The recent White House report on advanced manufacturing was covered by BioPharma Reporter. One chapter of the report is dedicated to investment in regenerative medicine and challenges associated with it:
The Federal Government invested $2.89 billion between 2012-2014 in regenerative medicine, primarily for the development of therapeutic techniques and technologies.17 While there has been a steady increase in funding to demonstrate the possibility of regenerative biologic solutions to some vexing health concerns, there is a critical and growing need to focus on process engineering to achieve manufacturing reproducibility to increase the reach of the emerging therapeutics.
Another chapter higlights the areas of interest and potential future investment. Bioengineering for regeneratiove medicine and bioprintinng made in a list of US Government priorities.
8. New methods and protocols:
Bioengineering a 3D skin integumentary organ system from iPS cells (Sci Adv)
Large-scale production of megakaryocytes from human pluripotent stem cells (Nat Commun)
Tissue-specific differentiation potency of perinatal MSCs (Sci Rep)
Ex vivo expansion of cord blood CD34+ cells with MSC-derived microvesicles (Stem Cells Int)