Characterization and Function of Cryopreserved Bone Marrow from Deceased Organ Donors: A Potential Viable Alternative Graft Source

• Published in: Transplantation and cellular therapy 2023-02, Vol.29 (2), p.95.e1-95.e10
• Main Authors: Johnstone, Brian H., Woods, John R., Goebel, W. Scott, Gu, Dongsheng, Lin, Chieh-Han, Miller, Hannah M., Musall, Kelsey G., Sherry, Aubrey M., Bailey, Barbara J., Sims, Emily, Sinn, Anthony L., Pollok, Karen E., Spellman, Stephen, Auletta, Jeffery J., Woods, Erik J.
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow; CD34; Cryopreservation; Cryopreservation - methods; Hematopoietic Stem Cell Transplantation - methods; Humans; Living Donors; Mice; Murine Engraftment; Organ Donor; Prospective Studies; Vertebral Body
• ISSN: 2666-6367; 2666-6375; 2666-6367
• DOI: 10.1016/j.jtct.2022.11.010

Despite the readily available graft sources for allogeneic hematopoietic cell transplantation (alloHCT), a significant unmet need remains in the timely provision of suitable unrelated donor grafts. This shortage is related to the rarity of certain HLA alleles in the donor pool, nonclearance of donors owing to infectious disease or general health status, and prolonged graft procurement and processing times. An alternative hematopoietic progenitor cell (HPC) graft source obtained from the vertebral bodies (VBs) of deceased organ donors could alleviate many of the obstacles associated with using grafts from healthy living donors or umbilical cord blood (UCB). Deceased organ donor-derived bone marrow (BM) can be preemptively screened, cryogenically banked for on-demand use, and made available in adequate cell doses for HCT. We have developed a good manufacturing practice (GMP)-compliant process to recover and cryogenically bank VB-derived HPCs from deceased organ donor (OD) BM. Here we present results from an analysis of HPCs from BM obtained from 250 deceased donors to identify any substantial difference in composition or quality compared with HPCs from BM aspirated from the iliac crests of healthy living donors. BM from deceased donor VBs was processed in a central GMP facility and packaged for cryopreservation in 5% DMSO/2.5% human serum albumin. BM aspirated from living donor iliac crests was obtained and used for comparison. A portion of each specimen was analyzed before and after cryopreservation by flow cytometry and colony-forming unit potential. Bone marrow chimerism potential was assessed in irradiated immunocompromised NSG mice. Analysis of variance with Bonferroni correction for multiple comparisons was used to determine how cryopreservation affects BM cells and to evaluate indicators of successful engraftment of BM cells into irradiated murine models. The t test (with 95% confidence intervals [CIs]) was used to compare cells from deceased donors and living donors. A final dataset of complete clinical and matched laboratory data from 226 cryopreserved samples was used in linear regressions to predict outcomes of BM HPC processing. When compared before and after cryopreservation, OD-derived BM HPCs were found to be stable, with CD34+ cells maintaining high viability and function after thawing. The yield from a single donor is sufficient for transplantation of an average of 1.6 patients (range, 1.2 to 7.5). CD34+ cells from OD-derived HPCs from BM pr