The University of Michigan School of Dentistry
Hematopoietic stem cells (HSCs) are the most therapeutically exploited adult stem cells, used routinely to treat leukemia and hematologic disease via HSC transplantation. Every year in the United States, 20,000 HSCTs are performed. However, problems remain with this treatment.
Transplantation requires donor HSCs to engage with the proper supporting niche, survive, proliferate, and differentiate into mature blood cells. Not all patients have access to suitable donors. Immunological complications, such as graft-versus-host disease, contribute to high morbidity and mortality rates. For donors, the vast majority of transplants use HSCs from mobilized peripheral blood (mPB). Collecting HSCs from mPB requires a multi-day treatment, which comes with high rates of grade 4 and 5 side effects, including debilitating bone pain, headache, malaise, nausea, sub-febrile body temperature and night sweats. About 50% of contacted donors decline to donate and about half of those who decline do so because of fear of side effects or the inconvenience of spending days in the hospital for cell collection. Illuminating new molecular regulators of HSC transplantation can inform efforts to improve current HSC-based therapies by improving the efficiency of both transplant and collection of donor HSCs. Improved efficiency could reduce HSCs numbers required per transplant, easing the donation process. This could also allow for increased use of cord blood HSCs, which are currently limited in application due to delayed engraftment kinetics that largely result from small cell numbers.
In summary, HSC transplantation is an excellent therapeutic approach, extensively use to treat hematopoietic pathologies, but it is still far to be perfect. Thus, in the Morales-Hernández lab, we want to have a better understanding of the intrinsic and extrinsic factors that control HSC self-renewal, stemness, homing, engraftment, and hematopoietic reconstitution, which could lead to novel strategies to overcome challenges currently facing HSC transplantation.
Antonio Morales-Hernández Lab
Department of Periodontics and Oral Medicine
University of Michigan School of Dentistry
1011 N University Ave, Office: 2213 and Lab: 2310A
Ann Arbor 48109-1078, MI