Engrafted Stem Cells Promote Cascade Migration of Circulating Stem Cells via SDF-1a Pathway in Ischemic Tissue
Shuang-Bai Zhou, M.D., Ph.D., Si-Zheng Zhou, M.D., Kai Liu, M.D., Ph.D., Cheng-An Chiang, M.D., Ph.D., Qing-Feng Li, M.D., Ph.D..
Shanghai Jiao Tong University, Shanghai Ninth People's Hospital, Shanghai, China.
During the past years, mesenchymal stem cells (MSCs) are reported to be recruited to the ischemic tissue and contribute to vascularization. Though the mechanism of migrated MSCs toward vascularization has been reported, the influence of these engrafted MSCs to the circulating stem cells is unclear. Here we discuss the affect of engrafted MSCs in ischemic tissue toward the circulating MSCs.
Expression of SDF-1a in hypoxic cultured MSCs was evaluated. MSCs from luciferase-Tg Lewis rats were transplanted intravenously into a rat lower limbhind ischemic model, while wild type MSCs pretreated with/without SDF-1a shRNA were transplanted intramuscularly to ischemic tissue (MSC Engrafted Group/ SDF-1aneg MSC Engrafted Group). The blood perfusion was evaluated with FLPI. The migration of circulating Luc-MSCs was tracked in vivo continuously by luminescence imaging. Hindlimb muscle sections were stained with anti-CD31, SDF-1a antibodies, and anti-luciferase antibody, to mark migrated MSCs.
SDF-1a expression was upregulated in MSCs under hypoxic culture and also found in engrafted MSCs in ischemic tissue. The bioimaging results showed that circulating MSCs migrated earlier in MSC Engrafted Group than Control Group. When blocking SDF-1a pathway in engrafed MSCs, the migration of circulating MSC was no significant different as in control group. FLPI results showed that vascularization was significantly slowed when blocking SDF-1a pathway in engrafted MSCs. Immunohistologic staining showed that less migrated Luc-MSCs were found in ischemic tissue when engrafted MSC’s SDF-1a pathway was blocked.
Engrafted MSCs produce SDF-1a in ischemic tissue promoting migrating cascade of circulating MSCs and accelerate vascularization.
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