Human Umbilical Cord Blood-Derived Stromal Cells Are Superior to Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Inducing Myeloid Lineage Differentiation In Vitro

Abstract

Stromal cells and mesenchymal stem cells (MSCs), 2 important cell populations within the hematopoietic microenvironment, may play an important role in the development of hematopoietic stem/progenitor cells. We have successfully cultured human umbilical cord blood-derived stromal cells (hUCBDSCs). It has been demonstrated that MSCs also exist in hUCB. However, we have not found any reports on the distinct characteristics of hUCBDSCs and human umbilical cord blood-derived mesenchymal stem cells (hUCBDMSCs). In this study, hUCBDSCs and hUCBDMSCs were isolated from the cord blood of full-term infants using the same density gradient centrifugation and cultured in the appropriate medium. Some biological characteristics and hematopoietic supportive functions were compared in vitro. hUCBDSCs were distinct from hUCBDMSCs in morphology, proliferation, cell cycle, passage, immunophenotype, and the capacity for classical tri-lineage differentiation. Finally, quantitative real-time polymerase chain reaction analysis revealed that granulocyte colony-stimulating factor (G-CSF) gene expression was higher in hUCBDSCs than that in hUCBDMSCs. Enzyme-linked immunosorbent assay revealed that the secretion of G-CSF, thrombopoietin (TPO), and granulocyte macrophage colony-stimulating factor (GM-CSF) by hUCBDSCs was higher than that by hUCBDMSCs. After coculture, the granulocyte/macrophage colony-forming units (CFU-GM) of hematopoietic cells from the hUCBDSC feeder layer was more than that from the hUCBDMSC feeder layer. Flow cytometry was used to detect CD34+ hematopoietic stem/progenitor cell committed differentiation during 14 days of coculture; the results demonstrated that CD14 and CD33 expression in hUCBDSCs was significantly higher than their expression in hUCBDMSCs. This observation was also true for the granulocyte lineage marker, CD15. This marker was expressed beginning at day 7 in hUCBDSCs. It was expressed earlier and at a higher level in hUCBDSCs compared with hUCBDMSCs. In conclusion, hUCBDSCs are different from hUCBDMSCs. hUCBDSCs are superior to hUCBDMSCs in supporting hematopoiesis stem/progenitor cells differentiation into myeloid lineage cells at an early stage in vitro.

Adipose tissue‑derived stem cells modulate immune function in�vivo and promote long‑term hematopoiesis in�vitro using the aGVHD model

“…Arthur et al (29) reported that Twist-1-overexpressing BMSCs exhibited an enhanced capacity in maintaining human CD34 + hematopoietic stem cells (HSCs) in long-term culture-initiating cell (LTC-IC) assays. It was also confirmed that MSCs support the proliferation of hematopoietic stem/progenitor cells in vitro by coculture of human umbilical cord blood mononuclear cells and umbilical cord mesenchymal stem cells for 14 days (30). Few studies have demonstrated that ADSCs support the long-term proliferation of hematopoietic stem/progenitor cells.…”

Dissection of the Cord Blood Stromal Component Reveals Predictive Parameters for Culture Outcome

“…Yet, it is not clear why perivascular cells should abandon their niche and should be circulating in cord blood. In addition, cord blood was reported to give rise to distinct stromal populations in terms of morphology, isolation frequency, proliferation rate, differentiation potentialities, and surface markers [23][24][25][26].…”

Infusion of allogeneic umbilical cord blood hematopoietic stem cells in patients with chemotherapy-related myelosuppression

“…UCB has been shown to be abundant in hematopoietic growth factors, including G-CSF (16), GM-CSF (5), EPO (16), IL-2 (16), IL-6 (16,17), insulin-like growth factors (18) and steel factor (7). The expression levels of these growth factors are significantly higher in UCB compared with the peripheral blood.…”

“…Traditional allogeneic UCB-HSC transplantation requires partial human leukocyte antigen (HLA) matching, ablation of the recipient’s marrow and immunosuppression following transplantation (5,6). These requirements significantly limit the broad application of UCB-HSC transplantation in patients with chemotherapy-related myelosuppression.…”

“…In 1988, Dr Eliane Gluckman successfully treated a child with Fanconi anemia by performing the first umbilical cord blood (UCB) hematopoietic stem cell (HSC) transplantation, which demonstrated that UCB-HSC transplantation may be a promising tool for the treatment of blood system impairments ( 3 , 4 ). Traditional allogeneic UCB-HSC transplantation requires partial human leukocyte antigen (HLA) matching, ablation of the recipient’s marrow and immunosuppression following transplantation ( 5 , 6 ). These requirements significantly limit the broad application of UCB-HSC transplantation in patients with chemotherapy-related myelosuppression.…”