An independent study cites the use of HemaCare-sourced human bone marrow-derived CD34+ stem cells for research into a potential new therapy for sickle cell disease. 
Sickle cell is a serious disease that affects millions of people throughout the world. People affected by sickle cell anemia have rigid, sickle-shaped red blood cells that can’t adequately carry oxygen to the body’s tissues. As a result, sickle cell patients suffer from a variety of medical complications, which can shorten their life span. Contemporary cell therapy treatments have focused on a gene therapy approach that uses lentiviral vectors to supply CD34+ bone marrow-derived stem cells with an unimpaired version of the hemoglobin gene. While this tactic has met with some promise, finding healthy, matched bone marrow donors is difficult. Researchers at Biogen, a well-known biotech firm headquartered in Cambridge, Massachusetts, are trying to discover cell and gene therapy methods that they hope will provide an alternative solution, and thereby improve treatment success rates.
The Cambridge-based scientists are basing their new method on the premise that a better approach might be to reactivate fetal γ-globin while reducing defective adult β-globin expression. This would involve disrupting a gene who’s only known function appears to be mediating the switch between fetal to adult type globin. The research group hopes that this will limit any harmful side effects.
To set their research in motion, the authors obtained bone marrow samples from healthy volunteers in HemaCare’s tissue donor network. HemaCare maintains the industry’s largest donor pool, which improves the chances of finding healthy matched donors. CD34+ bone marrow-derived stem cells were isolated from the bone marrow tissue, then cryopreserved in CryoStor® CS10 (BioLife Solutions) for further work. Later, the researchers targeted the desired gene sequence with a type of artificial restriction enzyme that can cut DNA at a specific site. Two experiments were carried out; in one case, the target gene was completely inactivated, while in the other case, gene function was disrupted, but not completely knocked out.
The results were quite interesting. In the situation where gene function was entirely knocked out, stem cells had reduced engraftment potential, and reduced ability to differentiate into red blood cells. In the case where a genetic target site was chosen that disrupted but did not eliminate gene function, stem cells formed fully functional red blood cells that were capable of robust long-term engraftment in a mouse model. The authors are expanding their work, and hope one day they’ll see similar results in humans. HemaCare researchers hope to continue to support this work and similar efforts through into clinical development. If you are interested to learn about how HemaCare can help with your research, please contact (877) 397-3087.
- Chang K., et al. Long-Term Engraftment and Fetal Globin Induction upon BCL11A Gene Editing in Bone-Marrow-Derived CD34+ Hematopoietic Stem and Progenitor Cells. Molecular Therapy: Methods and Clinical Development. 4:137-148. Mar 2017