Reconstruction of Hematopoietic Inductive Microenvironment after Transplantation of VCAM-1-Modified Human Umbilical Cord Blood Stromal Cells

Abstract

The hematopoietic inductive microenvironment (HIM) is where hematopoietic stem/progenitor cells grow and develop. Hematopoietic stromal cells were the key components of the HIM. In our previous study, we had successfully cultured and isolated human cord blood–derived stromal cells (HUCBSCs) and demonstrated that they could secret hemopoietic growth factors such as GM-CSF, TPO, and SCF. However, it is still controversial whether HUCBSCs can be used for reconstruction of HIM. In this study, we first established a co-culture system of HUCBSCs and cord blood CD34 + cells and then determined that using HUCBSCs as the adherent layer had significantly more newly formed colonies of each hematopoietic lineage than the control group, indicating that HUCBSCs had the ability to promote the proliferation of hematopoietic stem cells/progenitor cells. Furthermore, the number of colonies was significantly higher in vascular cell adhesion molecule-1 (VCAM-1)-modified HUCBSCs, suggesting that the ability of HUCBSCs in promoting the proliferation of hematopoietic stem cells/progenitor cells was further enhanced after having been modified with VCAM-1. Next, HUCBSCs were infused into a radiation-damaged animal model, in which the recovery of hematopoiesis was observed. The results demonstrate that the transplanted HUCBSCs were “homed in” to bone marrow and played roles in promoting the recovery of irradiation-induced hematopoietic damage and repairing HIM. Compared with the control group, the HUCBSC group had significantly superior effectiveness in terms of the recovery time for hemogram and myelogram, CFU-F, CFU-GM, BFU-E, and CFU-Meg. Such differences were even more significant in VCAM-1-modified HUCBSCs group. We suggest that HUCBSCs are able to restore the functions of HIM and promote the recovery of radiation-induced hematopoietic damage. VCAM-1 plays an important role in supporting the repair of HIM damage.

Mesenchymal stromal cell-derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells

“…Many studies have demonstrated that the administration of MSC can protect and reverse radiation damage to bone marrow 15–17 or other tissues 36–42 . However, the mechanisms underlining these beneficial effects are largely unknown and controversial.…”

Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia

“… 31 32 3) UCBI offers a large amount of G-CSF, GM-CSF, and CFU-F to increase the recovery of SAA. 21 22 23 24 25 26 27 It was noteworthy that intervals from first diagnosis to IST at baseline was longer in the UCBI+IST group than the IST group. The detailed reasons were as follows.…”

“… 21 22 23 24 3) Colony forming unit-fibroblastic (CFU-F) in UCB, which plays a critical role in hematopoietic microenvironment, improves the recovery of hematopoiesis. 25 26 27 4) HSCs from UCB are characterized by weak antigenicity that decreases the risk of GVHD. 28 These findings confirm the utility of UCB in various hematologic diseases, and considering the pancytopenia syndrome as the key property of SAA, we hypothesized that UCB could realize a good efficacy in treating SAA patients.…”

Increased expression of CX43 on stromal cells promotes leukemia apoptosis

“…The sections were then stained with DAPI and examined with fluorescence microscope. The Hemapun 948 cold vacuum embedding technique was used to prepare Bone marrow sections [ 2 ] : Bone marrow pathological tissues was fixed in pre-cooled 4°C Bouin fixative solution for 1 h, washed with 0.1 ml/L sodium dimethylarsinate buffer in a 4°C refrigerator for 30 min, and dehydrated at 4°C in a gradient of alcohol concentrations for 10 min in each concentration. Living tissue blocks were then placed on the bottom of a mold with 2 ml of solution A in a type 1354 vacuum dryer for 2–4 h at 4°C.…”

“…Although the survival rate of leukemia has been greatly improved due to new drugs, relapse of leukemia from minimal residue disease (MRD) remains a clinical challenge. The remaining leukemia stem cells in bone marrow (BM) following radiotherapy and/or chemotherapy are the primary cause for minimal residual disease (MRD) [ 1 , 2 ]. Therefore, modifying the BM microenvironment upon which leukemic stem cells depend for existence is a potential novel therapeutic strategy with less toxicity in the treatment of leukemia.…”