Clinical application of hematopoietic progenitor cell expansion: current status and future prospects

Abstract

Summary:In the past decade, we have witnessed significant advances in ex vivo hematopoietic stem cell culture expansion, progressing to the point where clinical trials are being designed and conducted. Preclinical milestone investigations provided data to enable expansion of portions of hematopoietic grafts in a clinical setting, indicating safety and feasibility of this approach. Data derived from current clinical trials indicate successful reconstitution of hematopoiesis after myeloablative chemoradiotherapy using infusion of ex vivo-expanded perfusion cultures. Future avenues of exploration will focus upon refining preclinical and clinical studies in which cocktails of available cytokines, novel molecules and sophisticated expansion systems will explore expansion of blood, marrow and umbilical cord blood cells.

Ionizing Radiation Enhances the Engraftment of Transplanted In Vitro–Derived Multipotent Astrocytic Stem Cells

“…Isolated cells are then subjected to culture conditions that will produce NSs, indicating that the cell population isolated contains NSCs. In the field of hematopoiesis, attempted in vitro manipulation and subsequent expansion of cultured HSCs has been shown to result in decreased pluripotency and engraftment by the HSC, with only hematopoietic progenitor cells lacking the capacity for functional reconstitution being successfully expanded in vitro [39], in theory due to the incom- plete reconstruction of the bone marrow microenvironment in vitro. Transplantation of noncultured, primary HSCs isolated from donor bone marrow still yields the most robust, long-term engraftment into the niche, and it is entirely possible that the in vitro manipulation of NSCs will result in a similar loss of multipotency and engraftment ability.…”

Hematopoetic stem cell transplantation in children

“…When compatibility of human leukocyte antigens is also considered, the recommended cell dose is >3.0x10 7 /kg for 6/6 HLA compatible cord blood, >4.0x10 7 /kg for 5/6 HLA compatible cord blood and >5.0x10 7 /kg for 4/6 HLA compatible cord blood (16). In recent years, applications directed to increase the low cell number which is the major problem in cord blood transplantation have been tried including ex-vivo expansion, transplantation with double cord blood and peripheral blood stem cell infusion from the same donor simultaneously with cord blood transplantation (17)(18)(19)(20)(21)(22). In cord blood, compatibility for HLA-A and HLA-B at the antigen level (low or moderate resolution) and compatibility for HLA-DRB1 at the allele level are considered standard compatibility.…”

Adult umbilical cord blood transplantation: a comprehensive review

“…51 Interestingly, Shpall et al reported a median four-fold increase in the CD34 þ cells, and explored both immediate and delayed infusion of the expanded cells. However, they failed to demonstrate a significant difference in terms of engraftment.…”

“…Although not the primary objective of this study (all trials were designed to address the primary endpoint of safety), incidence of both acute and cGVHD was high, and survival was relatively poor owing to high TRM and relapse rates in the high-risk populations enrolled. 51 Hence, too little clinical information is currently available to fully understand the safety and efficacy of ex vivo expansion culture of UCB. Of note, however, pre-clinical data suggest superior engraftment capacity of UCB progenitor cells compared to BM and peripheral blood stem cells, thus perhaps signifying that these cells still represent optimal targets for ex vivo expansion.…”