Stem Cells Dev. 2016 Dec 21. doi: 10.1089/scd.2016.0186. [Epub ahead of print]

Increasing stem cell dose promotes post-transplant immune reconstitution.

Xu N¹, Shen S², Dolnikov A^3,4.

Abstract

Umbilical Cord Blood (UCB) transplantation can provide a successful therapeutic option for patients that have no suitable related donor. UCB transplantation is often limited by the relatively small haematopoietic stem cell (HSC) numbers in UCB especially for adult recipients. Early neutrophil and platelet engraftment correlates with the stem cell numbers in UCB transplant. Compared to other HSC sources, immune reconstitution following UCB transplant is slower and complicated by increased frequency of opportunistic infections. The effect of HSC numbers in UCB transplant on immune reconstitution was not thoroughly examined. Using immunocompromised mice transplanted with purified UCB CD34+ stem cells we have demonstrated that increasing the numbers of CD34+ cells in the transplant promotes haematopoietic and immune reconstitution. At early stages post-transplant, high stem cell dose generated relatively more B cells while lower dose generated more myeloid and T cells. Thus, the size of the stem cell graft appears to modulate the differentiation potential of infused stem cells. Additionally, increasing stem cell dose in the transplant improved CD8+ T cell development and delayed late memory T cell skewing in expense of naive T cells highlighting the importance of HSC dose to maintain the pool of naive T cells able to develop strong immune responses. Transplantation of ex vivo expanded CD34+ cells did not promote but rather delayed immune reconstitution suggesting the loss of primitive lymphoid precursor cells during ex vivo expansion.