4.7 Article

Human kidney-derived hematopoietic stem cells can support long-term multilineage hematopoiesis

Journal

KIDNEY INTERNATIONAL
Volume 103, Issue 1, Pages 70-76

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2022.08.024

Keywords

chimerism; hematopoietic stem and progenitor cells; kidney allograft

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Long-term multilineage hematopoietic donor chimerism can occur in patients who receive a transplanted solid organ with lymphoid tissues, such as the intestine or liver. However, there is currently no evidence for kidney-resident hematopoietic stem cells in any mammal species. In this study, we found that human kidney-derived hematopoietic stem cells can reside in the recipient's bone marrow and replace host counterparts, leading to full donor chimerism of both lymphoid and myeloid lineages.
Long-term multilineage hematopoietic donor chimerism occurs sporadically in patients who receive a transplanted solid organ enriched in lymphoid tissues such as the intestine or liver. There is currently no evidence for the presence of kidney-resident hematopoietic stem cells in any mammal species. Graft-versus-host-reactive donor T cells promote engraftment of graft-derived hematopoietic stem cells by making space in the bone marrow. Here, we report full (over 99%) multilineage, donor-derived hematopoietic chimerism in a pediatric kidney transplant recipient with syndromic combined immune deficiency that leads to transplant tolerance. Interestingly, we found that the human kidney-derived hematopoietic stem cells took up long-term residence in the recipient's bone marrow and gradually replaced their host counterparts, leading to blood type conversion and full donor chimerism of both lymphoid and myeloid lineages. Thus, our findings highlight the existence of human kidney-derived hematopoietic stem cells with a self-renewal ability able to support multilineage hematopoiesis.

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