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. Good news about eye stem cell trials
Beginning of long-awaited embryonic stem cell-based trial for macular degeneration in UK, made the biggest splash in the media this week. The trial is a part of London Project to Cure Blindness – 10-year old initiative of University College London. The trial is sponsored by Pharma giant Pfizer. The first patient was treated a month ago and doing well.
By December, doctors will know whether the woman, who has age-related macular degeneration, has regained her sight after a successful operation at Moorfields Eye Hospital in London last month. Over 18 months, 10 patients will undergo the treatment.
Yet another exciting news is one year follow-up from the single case iPS cell-based trial in Japan. No tumors, no disease progression:
“The swelling of the retina is going down and the reoccurrence of abnormal blood vessels, which cause the disease, cannot be seen,” said Yasuo Kurimoto, general manager for ophthalmology at the Institute of Biomedical Research and Innovation Hospital in Kobe.
“The patient’s eyesight [which was gradually weakening before the operation] has been maintained since the operation,” said Kurimoto, who performed the operation.
Takahashi said, “Amid international attention over whether the patient would develop cancer, we are glad we could confirm that she has not.”
2. Human MSC are doing better in serum-free media
@Thomas_Heathman and his colleagues from Loughborough University, published very interesting study on comparison of human mesenchymal stromal cell (MSC) expansion in FBS and serum-free media:
Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth rate (P < 0.001) and increased consistency between donors compared with FBS-based culture.
PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilization, in vitro colony-forming potential and osteogenic potential despite the higher number of population doublings.
3. New self-assembling material for tissue engineering
Researchers described a method for self-assembly of tubular structures from bioinspired protein/peptide system. No bioprinting required! From press release:
The method uses solutions of peptide and protein molecules that, upon touching each other, self-assemble to form a dynamic tissue at the point at which they meet. As the material assembles itself it can be easily guided to grow into complex shapes.
Self-assembled tubular structures supported growth of mesenchymal stromal and endothelial cells. The next step is in vivo experiments.
Our system provides a leap forward by enabling the fabrication of geometrically complex scaffolds solely by directed self-assembly and without the need for moulds or templates. In addition, hybrid structures that enable the use of proteins offer tunability and a higher level of scaffold complexity, versatility and functionality.
4. Failure in cancer stem cell targeting
Boston-based company Verastem, halted cancer stem cell targeting trial for futility. As claimed by a company their experimental drug VX-6063 is targeting cancer stem cells in mesothelioma. VX-6063 is a FAK pathway inhibitor, described by MIT Professor Robert Weinberg as an important player in epithelial-mesenchymal transition. Weinberg is on Verastem’s advisory board.
5. Leukemic stem cells arise from hematopoietic progenitors
In the recent study, published online in Cell Stem Cell, researchers demonstrated that leukemic stem cells arise from mutated progenitor cells rather than from normal hematopoietic stem cells:
Using C/EBPa KO mice with the MF9 and MOZ-TIF2 leukemia models, we demonstrate that block of the CMP-GMP transition completely abrogates MF9-induced LSC formation and AML, regardless of the origin being from HSCs or myeloid progenitors.
…we show that the absence of LSC formation and the failure of leukemia development are a result of the block in myeloid differentiation, rather than the absence of C/EBPa per se.
6. Importance of sorting T-cell subsets in generation of therapeutic CAR T-cells
Riddell’s group from Fred Hutchinson Cancer Research published very important study for CAR T-cell field. They demonstrated that sorting of T-cell subsets allows to generate the most therapeutically potent and uniform CAR T-cell product:
We show that CAR-T-cell products generated from defined T-cell subsets can provide uniform potency compared with products derived from unselected T-cells that vary in phenotypic composition. These findings have important implications for the formulation of T-cell products for adoptive therapies.
7. Hypoxic culture conditions differently affects bone marrow and adipose-derived MSC
Very interesting study was published this week in online version of Stem Cells. Hypoxic culture condition is currently widely used technique across labs. However, hypoxia could promote genomic instability. Researchers compared genomic stability of clinical-grade human mesenchymal stromal cells, derived from bone marrow and adipose tissue, expanded with platelet lysate in hypoxiic conditions:
We conclude that long-term cultures under 1% O2 were more suitable for BM-MSCs as suggested by improved genomic stability compared with ADSCs.
8. New methods and protocols:
Transplantation of vascular bone marrow niche cells to enhance hematopoiesis (Stem Cell Reports)
Printing of decellularized extracellular matrix bioink (Nat Commun)
iPS cell-derived neuronal cells cultured on hydrogels for detection of Botulinum neurotoxin (Sci Reports)
Crestospheres: A method for maintenance of neural crest stem cells (Stem Cell Reports)
New effective and faster method to decellularize and recellularize the kidney (Oncotarget)
Interspecific in vitro assay for the chimera-forming ability of human pluripotent stem cells (Development)
9. Fresh reviews:
Enzymatic and non-enzymatic isolation of adipose tissue-derived cells (Cell Regen)
Clinical Trials with Mesenchymal Stem Cells: An Update (Cell Transplant)