Comparison of cord blood CD34 + stem cell expansion in coculture with mesenchymal stem cells overexpressing SDF‐1 and soluble /membrane isoforms of SCF

Abstract

Aim Umbilical cord blood hematopoietic stem cells (UCB HSCs) have been considered for the treatment of hematological malignancies due to their noninvasive collection, greater capacity of expansion, and remarkable tolerance for HLA mismatch in transplantation. On the other hand, the most considerable limitation of these cells is their inadequate amount of CD34 + HSCs which leads to delayed engraftment. The aim of this study was the expansion of CD34 + HSCs by coculturing with mesenchymal stem cells (MSCs) overexpressing stromal cell‐derived factor‐1, soluble and membrane isoforms of stem cell factor (sSCF/mSCF). Keeping structure and function of overexpressed cytokines by MSCs was expected which could beneficially affect the CD34 + HSC expansion. Methods MSCs and CD34 + HSCs were isolated from UCB mononuclear cells. UCB MSCs were nucleofected with one or more of sSCF, mSCF, and SDF‐1 expression vectors. Isolated CD34 + HSCs were then cocultured with nucleofected MSCs in 10 groups in culture medium containing TPO and Flt3L with or without SCF (3F or 2F groups). Then the CD34 + HSCs numeration, clonogenic capacity, and transcriptional levels of well‐known HSCs regulatory and stemness genes (CXCR4, HOXB4, BMI1, and SALL4) were assessed following coculture with modified MSCs. Results CD34 + HSCs which expanded on MSCs overexpressing mSCF/sSCF/SDF‐1 in the 3F group showed the most significant increase in the expansion (4.73 ± 0.26 fold), clonogenic capacity (5.3 ± 0.25 fold) and also transcriptional levels of CXCR4, HOXB4, and BMI1 (3.49 ± 0.13, 9.49 ± 0.78, and 11.6 ± 0.9 fold), respectively ( P < 0.05). Conclusion Overexpression of SCF and SDF‐1 by UCB MSCs in coculture system has efficient effect on UCB HSCs expansion. Furthermore nucleofected MSC overexpressing either sSCF/mSCF or mSCF/ sSCF /SDF‐1 could substitute the rhu SCF in HSC expansion culture medium.

Biological Characteristics of Umbilical Cord Mesenchymal Stem Cells and Its Therapeutic Potential for Hematological Disorders

“…SDF-1 could inhibit apoptosis of stem cells and was associated with hematopoietic stem cell proliferation and survival, which indicated that UC-MSCs have weak hematopoietic supportive capacity than BM-MSCs. Overexpression of SCF and SDF-1 by UC-MSCs in coculture system has efficient effect on the expansion of UCB-HSCs ( Ajami et al, 2019 ).…”

The Race of CAR Therapies: CAR-NK Cells for Fighting B-Cell Hematological Cancers

“…Finally, hiPSCss constitute a source for NK cells, as do CD34+ cells from umbilical cord blood, since these cells could have therapeutic uses apart from hematopoietic stem cell transplantation [110,111]. They have been taken into consideration, as they could provide a large number of NK cells [112,113], already extensively described [114].…”

DNA barcode to trace the development and differentiation of cord blood stem cells (Review)

“…Zhou et al (33) demonstrated that the combination of activin inhibitors and MEK/ERK inhibitors increased the induction rate of UCBSCs. The current focus is to identify a feeder-free culture system that is able to maintain the normal karyotype of the cells (34). Naka et al (35) demonstrated that retaining the culture system in a state of low oxygen pressure reduces the differentiation of UCBSCs and the development of chromosomal abnormalities (36).…”