Safety and Efficacy of Ex Vivo Expanded CD34 Stem Cells in Murine and Primate Models

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2019 Jun 15

PMID 31196160

Citations 8

Authors

Yu Zhang

Bin Shen

Xin Guan

Meng Qin

Zhihua Ren

Yupo Ma

Wei Dai

Xinxin Ding

Yongping Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Hematopoietic stem cell (HSC) transplantation has been widely applied to the treatment of malignant blood diseases. However, limited number of functional HSCs hinders successful transplantation. The purpose of our current study is to develop a new and cost-efficient medium formulation that could greatly enhance the expansion of HSCs while retaining their long-term repopulation and hematopoietic properties for effective clinical transplantation.

Methods: Enriched human CD34 cells and mobilized nonhuman primate peripheral blood CD34 cells were expanded with a new, cost-efficient expansion medium formulation, named hematopoietic expansion medium (HEM), consisting of various cytokines and nutritional supplements. The long-term repopulation potential and hematologic-lineage differentiation ability of expanded human cells were studied in the non-obese diabetic/severe combined immunodeficiency mouse model. Furthermore, the efficacy and safety studies were performed by autologous transplantation of expanded primate cells in the nonhuman primate model.

Results: HEM could effectively expand human CD34 cells by up to 129 fold within 9 days. Expanded HSCs retained long-term repopulation potential and hematologic-lineage differentiation ability, as indicated by (1) maintenance (over unexpanded HSCs) of immunophenotypes of CD38CD90CD45RACD49f in CD34 cells after expansion; (2) significant presence of multiple human hematopoietic lineages in mouse peripheral blood and bone marrow following primary transplantation; (3) enrichment (over unexpanded HSCs) in SCID-repopulating cell frequency measured by limiting dilution analysis; and (4) preservation of both myeloid and lymphoid potential among human leukocytes from mouse bone marrow in week 24 after primary transplantation or secondary transplantation. Moreover, the results of autologous transplantation in nonhuman primates demonstrated that HEM-expanded CD34 cells could enhance hematological recovery after myelo-suppression. All primates transplanted with the expanded autologous CD34 cells survived for over 18 months without any noticeable abnormalities.

Conclusions: Together, these findings demonstrate promising potential for the utility of HEM to improve expansion of HSCs for clinical application.

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