Expansion, Phenotype, and Function of Bone Marrow-Derived Mesenchymal Stromal Cells from Individuals with Sickle Cell Disease Open Access
Stenger, Elizabeth O'Brien (2016)
Hematopoietic cell transplantation (HCT) is the only curative therapy for sickle cell disease (SCD), but for the majority of patients who lack a matched donor, engraftment remains a significant barrier. Based upon dual function in promoting hematopoiesis and immunomodulation, mesenchymal stromal cells (MSCs) are an attractive cell-based therapy to modulate immunity and engraftment post-HCT. Studies have revealed limitations in approaches using cryopreserved, random donor MSCs, suggesting that fresh, autologous MSCs could circumvent these limitations. MSCs were expanded ex vivo from bone marrow (BM) samples from pediatric SCD patients and healthy adult volunteers. Doubling time of SCD MSCs was comparable to non-SCD MSCs. Phenotype of SCD MSCs, including flow cytometry for MSC surface markers and expression of indoleamine 2,3-dioxygenase (IDO) by RT-PCR, did not differ significantly to non-SCD MSCs. Non-SCD and SCD MSCs suppressed third-party and autologous (SCD) T cell proliferation in a dose-dependent manner. Expression of 47 hematopoiesis genes by Fluidigm array demonstrated minor differences by donor source and the potential to augment MSC expression by cytokine stimulation. These data demonstrate the feasibility of expanding autologous BM-derived MSCs from SCD patients. Importantly, phenotype and function of SCD MSCs are comparable to non-MSCs, supporting the use of autologous MSCs to enhance engraftment in SCD patients following haploidentical HCT.
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About this Master's Thesis
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|Expansion, Phenotype, and Function of Bone Marrow-Derived Mesenchymal Stromal Cells from Individuals with Sickle Cell Disease ()||2018-08-28 14:42:17 -0400||