Cryopreserved organ donor bone marrow achieves robust engraftment and chimerism in mismatched allogeneic transplantation
E.J. Woods, S. Munjal, M.H. Abidi, J. Pantin, V.L. Graves, H. Nowak, N. Weinstein, K. Blankenberger, K. Musall, P. Prasad, W.S. Goebel, B.H. Johnstone
Cytotherapy, (November 2025)
Summary: This study describes the development and validation of an organ donor–derived, cryopreserved bone marrow bank designed to provide an off-the-shelf alternative graft source for allogeneic hematopoietic stem cell transplantation (alloHCT). Using optimized processing controls cryopreservation methods, the authors demonstrate consistent long-term cell viability and functional potency, along with a >100% increase in yield per donor. Early clinical experience in three high-risk AML patients receiving 4/8 HLA-mismatched grafts demonstrated rapid neutrophil and platelet engraftment and full donor chimerism, supporting the feasibility of this approach to address unmet donor access and timing needs in alloHCT.
High-dose cryopreserved bone marrow from deceased donors may reduce relapse in HLA-mismatched allogeneic transplantation: Day 180 post-transplant HOPE update
S. Munjal, M. Abidi, J. Pantin, P. Prasad, V.L. Graves, W.S. Goebel, E.J. Woods
American Society of Hematology, (November 2025)
Summary: The preliminary findings from the first three evaluable patients (Day 180+) treated in the HOPE Expanded Access Program demonstrate that high-dose, cryopreserved hematopoietic cells from deceased donors is feasible and safe for infusion. Neutrophil and platelet engraftment occurred by Days 15–20 and 18–34, respectively. All three patients achieved 100% donor chimerism by Day 60. Acute GVHD (Grades 2–3) occurred in all three patients but was steroid-responsive and resolved. No cytokine release syndrome, viral reactivation, or chronic GVHD requiring systemic therapy occurred. The absence of relapse and chronic GVHD through Day 180, combined with manageable acute GVHD, highlights the potential of this novel graft source for patients with unmet needs.
Single cell transcriptional profiling of monocytes from asthma patients show a predisposition for an inflammatory response
K. Goss, M.L. Grant, L. Guglani, H. Miller, E.J. Woods
Cytotherapy, (October 2025). DOI: 10.1016/j.jcyt.2025.07.008
Summary: This study used single-cell RNA sequencing to compare blood monocytes from asthma patients and healthy controls, and to assess the effects of an infusion of interferon-γ–activated mesenchymal stromal cells (γMSCs) on asthmatic monocytes. Asthma patient monocytes showed elevated interferon response and viral defense gene expression, which were partially normalized following γMSC infusion, including reduced HLA Class I and interferon signaling genes. The findings suggest that γMSC therapy could modulate monocyte-driven inflammation and may benefit patients with poorly controlled asthma.
Allogenic Vertebral Body Adherent Mesenchymal Stromal Cells Promote Muscle Recovery in Diabetic Mouse Model of Limb Ischemia
T.S. Doiron, J. Stashevsky, N.Zhang, M. Yancey, C.H. Gil, H.D. Aridi, E.J. Woods, M.K. Madison, M.P. Murphy, S.J. Miller
Annals of Vascular Surgery, (January 2025). DOI: 10.1016/j.avsg.2024.08.004
Summary: In a diabetic mouse model of chronic limb-threatening ischemia (CLTI), intramuscular injection of allogeneic vertebral bone-adherent mesenchymal stromal cells (vBA-MSCs) improved limb perfusion, muscle function, and angiogenesis. Treated muscles showed reduced fibrosis and increased expression of genes associated with muscle regeneration, vascular growth, and anti-inflammatory immune responses. These results suggest that vBA-MSCs could be a promising therapeutic approach to restore muscle and vascular function in diabetic CLTI.
Identification of a fundamental cryoinjury mechanism in MSCs and its mitigation through cell-cycle synchronization prior to freezing
B.H. Johnstone, D. Gu, C.H. Lin, J. Du, E.J. Woods Cryobiology, (December 2023) DOI: 10.1016/j.cryobiol.2023.104592
Summary: Cryopreservation of mesenchymal stromal cells (MSCs) often impairs post-thaw viability and function, limiting their clinical use. This study found that MSCs in S phase are particularly sensitive to cryoinjury, and that temporarily arresting cells in G0/G1 via serum starvation prior to freezing prevents apoptosis and preserves immunomodulatory function. This approach offers a robust strategy to maintain MSC potency post-thaw without the complexities of cryorecovery or potential side effects of cytokine priming.
Accelerating cryoprotectant delivery using vacuum infiltration
Ryan J. Forcier et al
Cryobiology, (September 2023). DOI: 10.1016/j.cryobiol.2023.104558
Summary: The ability to cryopreserve bone marrow within the vertebral body (VB) would offer significant clinical and research benefits. However, cryopreservation of large structures, such as VBs, is challenging due to mass transport limitations that prevent the effective delivery of cryoprotectants into the tissue. To overcome this challenge, we examined the potential of vacuum infiltration, along with carbonation, to increase the penetration of cryoprotectants.
Characterization and Function of Cryopreserved Bone Marrow from Deceased Organ Donors: A Potential Viable Alternative Graft Source
B.H. Johnstone et al
Transplantation and Cellular Therapy, (November 2022). DOI: 10.1016/j.jtct.2022.11.010
Summary: 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.
Transplantation of Hematopoietic Stem and Progenitor Cells from Cadaveric Organ Donors Leads to Long-Term Multilineage Engraftment in NSG Mice
L. Breyer, H. Wang, D. Gu, B.H. Johnstone, H. Ma, E.J. Woods and M. Mapara
American Society of Hematology, (November 2022). DOI: 10.1182/blood-2022-169787,
Summary: Hematopoietic Stem and Progenitor Cells (HSPC) from cadaveric donors (CDs) have been used historically almost exclusively in the context of tolerance induction in combined bone marrow (BM) and solid organ transplantation. To date, no systematic study has addressed their functional long-term engraftment capacities. However, HSPC from banked CDs might be of high importance since they increase the still limited donor pool with on-demand availability as well as allow potential tolerance induction for patients undergoing combined transplantation.
Preservation and Storage of Cells for Therapy: Current Applications and Protocols
J.P. Acker et al
Cell Engineering and Regeneration, (June 2022). DOI: 10.1007/978-3-319-37076-7_68-1
Summary: In this chapter we consider the particular preservation storage procedures applied to a range of cell types used to produce cell-based medicines. Specifically, it deals with the scientific considerations for preserving each cell type and the kinds of cryopreservation protocols used to successfully preserve these different cell types. The cell types addressed include both those commonly in current use for patient treatment, such as whole blood and hematopoietic stem cells and also examples of new cell-based medicines including tissue progenitor cells (MSCs), (The use of the term Mesenchymal Stem Cell (MSC) has been hotly debated in the literature as it actually applies to several different cell types.
A Large-Scale Bank of Organ Donor Bone Marrow and Matched Mesenchymal Stem Cells for Promoting Immunomodulation and Transplant Tolerance
B.H. Johnstone, F. Messner, G. Brandacher, and E.J. Woods
Frontiers in Immunology, (February 2021). DOI: 10.3389/fimmu.2021.622604
Summary: Induction of immune tolerance for solid organ and vascular composite allografts is the Holy Grail for transplantation medicine. This would obviate the need for life-long immunosuppression which is associated with serious adverse outcomes, such as infections, cancers, and renal failure. Currently the most promising means of tolerance induction is through establishing a mixed chimeric state by transplantation of donor hematopoietic stem cells; however, with the exception of living donor renal transplantation, the mixed chimerism approach has not achieved durable immune tolerance on a large scale in preclinical or clinical trials with other solid organs or vascular composite allotransplants (VCA). Ossium Health has established a bank of cryopreserved bone marrow (BM) to deal with this issue.
Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank
E.J. Woods, A.M. Sherry, J.R. Woods, J.W. Hardin, M. LaFontaine, G. Brandacher, and B.H. Johnstone
Journal of Translational Medicine, (August 2020). DOI: 10.1186/s12967-020-02470-1
Summary: Deceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. A challenge for a future BM banking system will be to manage the prolonged ischemia times that are inevitable when bones procured at geographically-dispersed locations are shipped to distant facilities for processing. In this study, we: (a) quantify, under realistic field conditions, the relationship between ischemia time and the quality of hematopoietic stem and progenitor cells (HSPCs) derived from deceased-donor BM; (b) identify ischemia-time boundaries beyond which HSPC quality is adversely affected; (c) investigate whole-body cooling as a strategy for preserving cell quality; and (d) investigate processing experience as a variable affecting quality.
Identification and characterization of a large source of primary mesenchymal stem cells tightly adhered to bone surfaces of human vertebral body marrow cavities
B.H. Johnstone, H.M. Miller, M.R. Beck, D. Gu, S. Thirumala, M. LaFontaine, G. Brandacher, E.J. Woods
Cytotherapy, (July 2020). DOI: 10.1016/j.jcyt.2020.07.003
Summary: Therapeutic allogeneic mesenchymal stromal cells (MSCs) are currently in clinical trials to evaluate their effectiveness in treating many different indications. Eventual commercialization for broad distribution will require further improvements in manufacturing processes to economically manufacture MSCs at scales sufficient to satisfy projected demands. We have discovered that an abundant population of cells possessing all the hallmarks of MSCs is tightly associated with the vertebral body (VB) bone matrix and only liberated by proteolytic digestion. Here we demonstrate that these vertebral bone-adherent (vBA) MSCs possess all the International Society of Cell and Gene Therapy-defined characteristics (e.g., plastic adherence, surface marker expression and trilineage differentiation) of MSCs, and we have therefore termed them vBA-MSCs. We have established this as a novel and plentiful source of MSCs that will benefit the cell therapy market by overcoming manufacturing and regulatory inefficiencies due to donor-to-donor variability.