Safety of mismatched cord blood transplantation in regenerative medicine

by Alexey Bersenev on August 11, 2010 · 0 comments

in clinical trials and cases

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Many people predict that unrelated allogeneic cord blood (CB) cell transplantation could be “the next big thing” in regenerative medicine. A few obvious questions arise here:

    1. Can we transplant HLA-mismatched CB cells into the patient with degenerative disease without fear of adverse immune reactions such as graft-versus-host (GVH) and host-mediated immune clearance? How many cells would be safe?
    2. Can we transplant allogeneic CB cells with a regenerative purpose without myeloablative or immunosuppressive conditioning?
    3. What therapeutic benefit would we expect after allogeneic CB cell therapy in immunocompetent (non-conditioned) patient?

All of these questions were addressed in the 2007 review – Cord blood in regenerative medicine: do we need immune suppression?

The possibility of using cord blood in absence of host preconditioning would open up the door for a multitude of stem cell therapeutic applications. The currently dogma amongst cord blood transplanters is that administration of allogeneic cord blood, even if HLA-matched, would in the best case scenario lead to immunologically-mediated rejection or the graft, and in the worst case cause GVHD. Here we provide rationale for the preliminary clinical exploration of cord blood administration in a non-preconditioned host.

The authors cite a lot of historical facts showing that CB cell transplant like a blood transfusion was done safely even in the 1930s, when HLA matching was not introduced. Reported data shows that even in myeloablative setting in leukemia clinic HLA-matching in CB transplant does not play a significant role in the outcome. The role of HLA-matching in CB cell transplantation for purposes of regenerative medicine has not been tested and reported. Now we have the first evidence, that mismatched allogeneic CB cell therapy can be done safely in different non-hematological conditions, which do not required immunosupressive conditioning.

The authors evaluated safety of allogeneic mismatched umbilical CB mononuclear cell therapy in 114 patients mostly with neurodegenerative diseases, which was performed in Nanshan Affiliated Hospital of Guangdong Medical College (China):

Doses of 1-3 x 107 cord blood mononuclear cells per treatment, with 4-5 treatments both intrathecal and intravenously were performed. Adverse events and hematological, immunological, and biochemical parameters were analyzed for safety evaluation.

Results: No serious adverse effects were reported. Hematological, immunological, and biochemical parameters did not deviate from normal ranges as a result of therapy.

and conclusion:

In summary, these data support the safety and freedom from immunologically-mediated adverse effects of allogeneic cord blood therapy in absence of immune suppression/myeloablation. This study presents for the first time a detailed safety analysis of using non-matched, allogeneic cord blood cells to treat non-hematopoietic degenerative conditions. The longest follow-up with this protocol was 4 years with no evidence of immune reactivity or GVHD. Evaluation of therapeutic benefit is currently in progress.

I’m really glad to see the first report like this. I think it’s very important and a good study. But I’d like to see at least one more independent report without any author’s conflict of interest. Also, the question of ABO-matching needs to be address further in regenerative medicine settings. I’d like to hear comments from hematologists and bone marrow transplantation physicians especially.

full text is freely available online (.pdf)

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