Cotransplantation of HLA-Identical Mesenchymal Stem Cells and Hematopoietic Stem Cells in Chinese Patients with Hematologic Diseases.

Background: Mesenchymal stem cells(MSCs) can be isolated from bone-marrow and expanded ex-vivo, may support hematopoietic reconstruction and mitigate graft-versus-host disease (GVHD) in hematopoietic stem cells transplantation (HSCT). We hope to explore the feasibility and safety of cotransplantation culture-expanded MSCs and hematopoietic stem cells (HSCs) from the same human leucocyte antigen (HLA)-identical sibling donor in patients with hematologic diseases.

Methods: Bone marrow mononuclear cells from healthy donors were cultured and expanded ex-vivo. Immunophenotype, karyotye, immunosuppressive property of the harvested MSCs were characterized. Patients were cotransplanted with HSCs and MSCs from the same donor. Hematopoietic reconstruction, complications and clinical outcomes after transplantation in these patients were observed.

Results: (1.77±0.40)×10⁶/kg (donor’s weight) MSCs were successfully expanded from 23.6±5.96ml bone marrow samples. They had normal karyotype and were CD73, CD90, CD105 positive and CD34, CD45, HLA-DR negative. They can inhibit mixed lymphocyte reactions (MLRs). Twelve patients were undergoing cotransplantation. No adverse response was observed during and after the infusion of allogenic MSCs. Hematopoietic reconstruction were rapid. Two patients developed grade II∼IV acute GVHD. Two patients developed systermatic chronic GVHD. Four patients suffered from cytomegalovirus (CMV) infection but were cured at last. Till now, seven patients have been alive for 29∼57 months and five patients died.

Conclusion: MSCs identified by immunophenotype analysis can be isolated from human bone marrow, expanded effectively by culture. Their quality and quantity are suitable for clinical use. It is safe and feasible to cotransplant patients with allogenic culture-expanded MSCs and HSCs.