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Reconstruction of hematopoietic inductive microenvironment after transplantation of VCAM-1-modified human umbilical cord blood stromal cells.

Liu Y, Chen XH, Si YJ, Li ZJ, Gao L, Gao L, Zhang C, Zhang X - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.

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.

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Dynamic observation of the nude mouse hemogram, bone marrow stromal CFU-F count, and bone marrow pathological slices after different doses of irradiation.4-A: WBC counts. 4-B: RBC counts. 4-C: Hemoglobin counts. 4-D: PLT counts. 4-E: CFU-F counts in bone marrow stromal cells, * compared with control, 3.5 and 5 Gy groups, P<0.01. 4-F: Nude mouse bone marrow pathological slices after 6.5 Gy irradiation. 4-G: Nude mouse bone marrow pathological slices after 8 Gy irradiation.
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pone-0031741-g004: Dynamic observation of the nude mouse hemogram, bone marrow stromal CFU-F count, and bone marrow pathological slices after different doses of irradiation.4-A: WBC counts. 4-B: RBC counts. 4-C: Hemoglobin counts. 4-D: PLT counts. 4-E: CFU-F counts in bone marrow stromal cells, * compared with control, 3.5 and 5 Gy groups, P<0.01. 4-F: Nude mouse bone marrow pathological slices after 6.5 Gy irradiation. 4-G: Nude mouse bone marrow pathological slices after 8 Gy irradiation.

Mentions: The changes in the hemogram differed among the nude mice that received the four different doses of irradiation. In the 3.5 Gy group, the white blood cell (WBC) and platelet (PLT) counts were the lowest on day +3, and the red blood cell (RBC) count was the lowest on day +5; after that, indicators of hemogram rapidly recovered. The WBC and PLT counts of the 3.5 Gy, 5 Gy, and 6.5 Gy groups were the lowest on day +5, and the RBC counts of the 5 Gy and 6.5 Gy groups were the lowest on day +7. The recovery in the 5 Gy group was faster than that in the 6.5 Gy group. One out of three nude mice died in the 6.5 Gy group. When the radiation dose increased to 8 Gy, the hematopoietic function of nude mice could not be recovered, which led to the death of nude mice, and experiments could not be continued (Fig. 4-A–E).


Reconstruction of hematopoietic inductive microenvironment after transplantation of VCAM-1-modified human umbilical cord blood stromal cells.

Liu Y, Chen XH, Si YJ, Li ZJ, Gao L, Gao L, Zhang C, Zhang X - PLoS ONE (2012)

Dynamic observation of the nude mouse hemogram, bone marrow stromal CFU-F count, and bone marrow pathological slices after different doses of irradiation.4-A: WBC counts. 4-B: RBC counts. 4-C: Hemoglobin counts. 4-D: PLT counts. 4-E: CFU-F counts in bone marrow stromal cells, * compared with control, 3.5 and 5 Gy groups, P<0.01. 4-F: Nude mouse bone marrow pathological slices after 6.5 Gy irradiation. 4-G: Nude mouse bone marrow pathological slices after 8 Gy irradiation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285638&req=5

pone-0031741-g004: Dynamic observation of the nude mouse hemogram, bone marrow stromal CFU-F count, and bone marrow pathological slices after different doses of irradiation.4-A: WBC counts. 4-B: RBC counts. 4-C: Hemoglobin counts. 4-D: PLT counts. 4-E: CFU-F counts in bone marrow stromal cells, * compared with control, 3.5 and 5 Gy groups, P<0.01. 4-F: Nude mouse bone marrow pathological slices after 6.5 Gy irradiation. 4-G: Nude mouse bone marrow pathological slices after 8 Gy irradiation.
Mentions: The changes in the hemogram differed among the nude mice that received the four different doses of irradiation. In the 3.5 Gy group, the white blood cell (WBC) and platelet (PLT) counts were the lowest on day +3, and the red blood cell (RBC) count was the lowest on day +5; after that, indicators of hemogram rapidly recovered. The WBC and PLT counts of the 3.5 Gy, 5 Gy, and 6.5 Gy groups were the lowest on day +5, and the RBC counts of the 5 Gy and 6.5 Gy groups were the lowest on day +7. The recovery in the 5 Gy group was faster than that in the 6.5 Gy group. One out of three nude mice died in the 6.5 Gy group. When the radiation dose increased to 8 Gy, the hematopoietic function of nude mice could not be recovered, which led to the death of nude mice, and experiments could not be continued (Fig. 4-A–E).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.

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.

Show MeSH
Related in: MedlinePlus