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Intra-bone Mesenchymal Stem Cell Injection Boosts Cord Blood Transplant in Adults

Review of "Phase I clinical trial of intra-bone marrow co-transplantation of mesenchymal stem cells in cord blood transplantation" from STEM CELLS Translational Medicine by Stuart P. Atkinson

Clinical studies in pediatric patients have demonstrated the feasibility and safety of cord blood transplantation with intravenous cotransplantation of mesenchymal stem cells (MSCs) to reduce the incidence of chronic graft‐vs‐host disease, hasten hematologic recovery, reduce graft failure rates, and decrease transplant‐related mortality [1-4].

To evaluate the utility of this approach in adult patients with hematologic disorders, researchers led by Makoto Murata (Nagoya University, Nagoya, Japan) designed a phase I trial of cord blood transplantation combined with an intra‐bone marrow injection of ex vivo expanded MSCs [5] to avoid trapping MSCs in the lungs following intravenous infusion [6, 7]. As reported in a recent STEM CELLS Translational Medicine article [8], Goto et al. now suggest that cotransplantation of MSCs may prevent graft‐vs‐host disease in adult human patients without negatively impacting cord blood engraftment.

The authors injected third-party MSCs into the bone marrow of five patients four hours before cord blood transplantation (with no adverse events related to the intra-bone marrow injection observed) and compared their recovery to six patients who received only cord blood transplantation. While all eleven patients achieved neutrophil, reticulocyte, and platelet recoveries over 20-30 days, three of the six cord blood transplantation only patients displayed grade II‐IV acute graft‐vs‐host disease compared to none of the MSC cotransplanted patients. Furthermore, all patients receiving cord blood transplantation with MSC cotransplantation survived without relapse to one year.

Together these data suggest that the intra-bone marrow transplantation of third-party MSCs represents an efficient means of improving cord blood transplantation; however, the authors also suggest that their cotransplantation strategy may also positively impact bone marrow- and peripheral blood-derived stem cell transplants.

For more on how intra-bone marrow injections of MSCs can safely boost cord blood transplantation, stay tuned to the Stem Cells Portal!

References

  1. MacMillan ML, Blazar BR, DeFor TE, et al., Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I–II clinical trial. Bone Marrow Transplantation 2009;43:447-454.
  2. Bernardo ME, Ball LM, Cometa AM, et al., Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation. Bone Marrow Transplantation 2011;46:200-207.
  3. Lee SH, Lee MW, Yoo KH, et al., Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation. Bone Marrow Transplantation 2013;48:1040-1045.
  4. Wu K-H, Sheu J-N, Wu H-P, et al., Cotransplantation of Umbilical Cord–Derived Mesenchymal Stem Cells Promote Hematopoietic Engraftment in Cord Blood Transplantation: A Pilot Study. Transplantation 2013;95.
  5. Goto T, Murata M, Terakura S, et al., Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol. Medicine 2018;97.
  6. Mabuchi Y, Morikawa S, Harada S, et al., LNGFR+THY-1+VCAM-1hi+ Cells Reveal Functionally Distinct Subpopulations in Mesenchymal Stem Cells. Stem Cell Reports 2013;1:152-165.
  7. Noort WA, Kruisselbrink AB, in't Anker PS, et al., Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34+ cells in NOD/SCID mice. Experimental Hematology 2002;30:870-878.
  8. Goto T, Murata M, Nishida T, et al., Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation. STEM CELLS Translational Medicine 2021;10:542-553.