RT info:eu-repo/semantics/article
T1 Influence of HLA Matching on the Efficacy of Allogeneic Mesenchymal Stromal Cell Therapies for Osteoarthritis and Degenerative Disc Disease
A1 García-Sancho Martín, Francisco Javier
A1 Sánchez García, Ana María de los Ángeles
A1 Vega Castrillo, Aurelio
A1 Noriega González, David César
A1 Nocito Colón, Mercedes
K1 HLA
K1 Antígeno leucocitario humano
K1 Human leukocyte antigen
AB The necessity for more effective therapies for chronic osteoarticular diseases has led to the development of treatments based on mesenchymal stem cells (MSCs), the natural precursors of musculoskeletal tissue. Treatments with autologous MSCs yielded excellent results, with nearly 70% improvement of pain and disability in osteoarthritis and degenerative disc disease. Using allogeneic MSCs is logistically more convenient and would widen the pool of eligible patients, but potential immune rejection should be considered. In this context, MSCs are purportedly immune evasive and better tolerated than other cell types.Methods We used samples collected during the performance of 2 randomized clinical trials using allogeneic bone marrow MSCs for treatment of osteoarthritis (NCT01586312) and degenerative disc disease (NCT01860417). Serum samples were used to determine anti-HLA antibodies, whereas either blood or MSC samples were used for HLA typing of recipients and donors, respectively. Algofunctional indexes were used as indicators of clinical evolution, and the correlation between the number of donor-host HLA mismatches and the efficacy of treatment was determined.Results Immune response was weak and transient, with reactivity decaying during the first year. Consistently, better donor-recipient HLA matching did not enhance efficacy.Conclusions This lack of reactivity is presumably due to the cooperation of 2 factors, (1) downregulation of the host immune responses by the transplanted MSCs and (2) effective insulation of these cells inside the articular cavity or the intervertebral disc, respectively. Interestingly, better HLA matching did not enhance efficacy. These observations have medical relevance as they support the clinical use of allogeneic cells, at least as a single-dose administration. Multiple-dose applications will require further research to exclude possible sensitization.
PB Lippincott, Williams & Wilkins
SN 2373-8731
YR 2017
FD 2017
LK http://uvadoc.uva.es/handle/10324/32543
UL http://uvadoc.uva.es/handle/10324/32543
LA eng
NO Transplantation Direct, 2017 - Volume 3 - Issue 9 - p e205
NO Producción Científica
DS UVaDOC
RD 21-may-2024