Human bone marrow mesenchymal stem cells expressing SDF-1 promote hematopoietic stem cell function of human mobilised peripheral blood CD34+ cells in vivo and in vitro.
OBJECTIVE
There is mounting evidence demonstrating that stromal cell derived factor-1 (SDF-1) plays an important role in homing of hematopoietic progenitor cells to bone marrow. This study was aimed to assess whether bone marrow mesenchymal stem cells overexpressing exogenous SDF-1 could synergistically promote the homing of CD34(+) (Cluster of Differentiation [CD]) cells to bone marrow of lethally irradiated severe combined immunodeficiency (SCID) mice.


METHODS
Human SDF-1 complementary Deoxyribonucleic acid (cDNA) was transfected into bone marrow-derived mesenchymal stem cells with recombinant lentiviral vector. The expression of SDF-1 was detected by real-time Polymerase Chain Reaction (PCR) and Enzyme-Linked Immunosorbent Assay (ELISA), and the ex vivo chemotaxis function on CD34(+) cells was measured by coculture system and Transwell system. SDF-1 gene-modified mesenchymal stem cell (MSC) and CD34(+) cells were infused into lethally irradiated SCID mice and the hematopoietic reconstitution in the recipient mice was examined.


RESULTS
Messenger ribonucleic acid (mRNA) and protein of SDF-1 in infected MSC were significantly higher than that of the non-infected control MSC (p < 0.05). The infected MSC have significant chemotaxis effect on CD34(+) cells in vitro and promote hematopoietic reconstitution after CD34(+) cell transplantation in vivo.


CONCLUSIONS
MSC with high-level expression of SDF-1 can synergistically promote hematopoietic reconstitution after CD34(+) cell transplantation in lethally irradiated SCID mice.
Liang
Xue
X
The Third Military Medical University, Department of Hematology, Xinqiao Hospital, Chongqing, China.
Su
Yong-Ping
YP
Kong
Pei-Yan
PY
Zeng
Dong-Feng
DF
Chen
Xing-Hua
XH
Peng
Xian-Gui
XG
Zou
Zhong-Min
ZM
Xu
Hui
H
D000818:Animals; D018952:Antigens, CD34 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002465:Cell Movement; D017690:Cell Transplantation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000235:genetics / Q000502:physiology; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental; D014162:Transfection
D018952:Antigens, CD34; D054377:Chemokine CXCL12; D012333:RNA, Messenger