Improving the Stamina and Effectiveness of Transplanted Stem Cells
Stem cell therapies that involve hematopoietic bone marrow transplants are currently being used to treat conditions such as sickle cell anemia, radiation damage, inherited metabolic damage, and cancers of the lymphatic system and blood.
The problem is, current bone marrow procedures have a low chance of success and can sometimes prove to be fatal due to the patient’s immune system rejecting the new cells, and graft-versus-host disease, where the marrow cells attack the healthy cells.
It was discovered that MSCs, or mesenchymal stromal cells, can nullify issues with bone marrow treatment by secreting materials that placate the immune system in animal trials. In clinical studies however, MSCs have failed to live up to their expectations, and encapsulation of the biomaterial has been unsuccessful so far.
But that may change, as a group of scientists from the Stem Cell Initiative at Harvard, John Paulson Applied Sciences and Engineering School, and Wyss Institute have found a new way to deliver MSCs using single-cell encapsulation technology that provides clearance from an immune attack and improves bone marrow procedures in mice. This report has been published in PNAS journal.
Angelo Mao, first author and former post-grad student in the Wyss Core Faculty and David Mooney, postdoc and lead author from Wyss Immuno-Materials Platform say that their breakthrough is the first single-cell encapsulation technology of its kind, one that’s now becoming popular in treating a variety of diseases. Mao also states that their cells may be frozen, then thawed with little to no impact on their performance, an important factor when it gets approved for treatment center and hospital use.
The team has built up on their previous work, which uses micro-fluidic vessels made up of alginate-based hydrogel, or ‘microgels’ to coat the bone marrow cells. The cells are encapsulated with 90 percent efficiency, while the material is small enough to be delivered intravenously. Encapsulated MSCs in mice were able to survive 10 times longer than bare stem cells and remained potent for 3 days.
The team’s next challenge was to determine how the microgel could affect the MSCs’ ability to work and resist attacks from the immune system. A new compound was added to the alginate material, which made the microgel ‘stiffer’ and able to resist internal clearing mechanisms and the subject’s immune system. MSCs were cultured after encapsulation to allow to multiply. When the new microgel material was introduced in mice subjects, the persistence was five times greater than the previous one and magnitudes better than bare stem cells.
The researchers incubated the cells within a fetal bovine serum medium to create an immune response before injecting them into mice. The new microgel material outperformed bare MSCs in mice that had pre-existing responses against stem cells. The team also tested their microgel and found that it did not hamper the MSCs’ performance compared to bare MSCs that were exposed to inflammatory cytokines.
The group then injected the microgel with MSCs with transplanted bone marrow, which was half allogeneic and half immune-compatible in mice subjects. After 9 days, mice that received MSC treatment had increased allogeneic bone marrow cells compared to control subjects. Moreover, there was a greater engraftment in the subjects’ bone marrow than the mice that didn’t get the injection.
Professor Mooney claims that one of the work’s strong points is its non-genetic aspect in increasing cell survival where needed, which could complement genetic engineering and is far more efficient than direct cell modification.
The Validation Project Program by Wyss Institute is a collaborative effort to finding possible solutions for treating ischemia, or blood vessel narrowing in human patients. Validation Projects are platforms that have the potential to be ground-breaking and have passed product development, intellectual property, concept refinement and pre-defined technical aspects.
Donald Ingber, Wyss Founding Director, SEAS Bioengineering professor, Judah Folkman Representative, and professor for the Boston Children’s Hospital’s Vascular Biology Program and HMS’ Vascular Biology Program, says that the technology is poised to solve current issues with stem cell therapy and bone marrow transplants using a bio-material approach that’s innovative and involves cross-disciplinary thinking, something that the institute values. The director further states that the team will get full support for the project as it advances to clinical trials and any application using the microgel technology for future cell and drug delivery methods.
To your health,
The Healing Miracle Team
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