In Utero Hematopoietic Cell Transplantation: Past Clinical Experience and Future Clinical Trials
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Purpose of Review
In utero hematopoietic stem cell transplantation is an evolving therapy with possible implications for the treatment of many fetal disorders. Here, we present the past clinical experience and current clinical trials and discuss future directions for in utero therapy.
Barriers to clinically meaningful in utero hematopoietic stem cell transplantation have been identified including maternal T cell-mediated graft rejection, achieving adequate space within the fetal bone marrow niche, and delivering adequate stem cells intravascularly. In a canine model of hematopoietic stem cell transplantation, high chimerism levels were achieved with maternal stem cells delivered intravascularly. Chimerism remained stable over a 2-year period without any evidence of graft-versus-host disease. Current clinical trials such as one for alpha thalassemia seek to apply these results in human diseases.
The field of in utero stem cell transplantation continues to improve and expand on the possible diseases that can be treated. The reasons for limited success in previous trials have been identified and current trials utilizing maternally derived stem cells at high doses are underway.
KeywordsIn utero hematopoietic stem cell transplantation Immune tolerance Fetal therapy Chimerism Stem cell niche
Compliance with Ethical Standards
Conflict of Interest
Russell G. Witt, Quoc-Hung L. Nguyen, and Tippi C. MacKenzie declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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