Lymphoid reconstitution of the human fetal thymus in SCID mice with CD34+ precursor cells.

TLDR

Human hematopoietic stem cell research has been limited by inadequate assay systems, and demonstrating T‑cell differentiation from precursor cells is difficult because cultured thymic stroma cells lose support for thymocyte maturation. The study aimed to characterize the differentiation potential of rare CD34+ fetal liver and bone marrow cells that display myeloid and pre‑B activity. The authors microinjected these CD34+ cells into HLA‑mismatched fetal thymus fragments partially depleted of hematopoietic cells by low‑temperature culture, then allowed the colonized thymuses to develop after engraftment into immunodeficient SCID mice. The modified SCID‑hu system demonstrated that even low numbers of fetal CD34+ progenitors can repopulate the lymphoid compartment of the human thymus.

Abstract

The search for human hematopoietic stem cells has been hampered by the lack of appropriate assay systems. Demonstration of the ability of precursor cell candidates to give rise to T cells is of significant difficulty since dissociated in vitro cultured thymus stroma cells lose their ability to sustain thymocyte maturation. To define further the differentiative capacities of the rare human fetal liver and bone marrow cells that express the CD34 surface antigen and exhibit in vitro myeloid and pre-B cell activities, we have microinjected them into HLA-mismatched fetal thymus fragments, partially depleted of hematopoietic cells by low temperature culture. In vitro colonized thymuses have then been allowed to develop upon engraftment into immunodeficient SCID mice. Using this modification of the SCID-hu system, we show that low numbers of fetal CD34+ progenitor cells can repopulate the lymphoid compartment in the human thymus.