Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

Abstract

Mesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isolation and re-culture of intravenously infused MSC. C57BL/6 MSC (500,000) constitutively expressing DsRed-fluorescent protein and radioactively labeled with Cr-51 were infused via the tail vein in wild-type C57BL/6 mice. After 5 min, 1, 24, or 72 h, mice were sacrificed and blood, lungs, liver, spleen, kidneys, and bone marrow removed. One hour after MSC infusion the majority of Cr-51 was found in the lungs, whereas after 24 h Cr-51 was mainly found in the liver. Tissue cultures demonstrated that viable donor MSC were present in the lungs up to 24 h after infusion, after which they disappeared. No viable MSC were found in the other organs examined at any time. The induction of ischemia-reperfusion injury in the liver did not trigger the migration of viable MSC to the liver. These results demonstrate that MSC are short-lived after i.v. infusion and that viable MSC do not pass the lungs. Cell debris may be transported to the liver. Long term immunomodulatory and regenerative effects of infused MSC must therefore be mediated via other cell types.

Conversion of Th17 into IL-17Aneg Regulatory T Cells: A Novel Mechanism in Prolonged Allograft Survival Promoted by Mesenchymal Stem Cell–Supported Minimized Immunosuppressive Therapy

“…Whereas previous reports have demonstrated that MSCs-not pertaining to their antigenicityare present in the spleen and liver when administered in the absence or before transplantation (25,39,41) and preferentially migrate to injury sites and localize in the graft after posttransplantation administration (25,42), we recently showed that MSCs are short-lived and fail to migrate beyond the lungs after i.v. infusion, although their debris is detectable in the liver (43 (44). This intermediary role of MDSCs is also in keeping with recent results from our group and others, demonstrating that MDSCs effectively promote Th17 cell differentiation and IL-17A production in various other models (45)(46)(47).…”

Annexin A1 Is a Key Modulator of Mesenchymal Stromal Cell–Mediated Improvements in Islet Function

“…Thus, although coengrafting islets and MSCs is technically feasible at the experimental kidney site, this obvious therapeutic strategy of cotransplanting islets and MSCs is confounded by the choice of the hepatic portal vein as the preferred clinical implantation site. Coinfused islets and MSCs disperse throughout the portal vasculature and are therefore unlikely to engraft together, with islets lodging in the hepatic microcirculation, whereas MSCs will most likely pass through the liver and engraft in the lung microcirculation (30). Because codelivering effective numbers of MSCs with the islet graft is not practical, an alternative strategy is to determine how MSCs influence islet function and devise mechanisms for delivering similar effects in an MSC-free system.…”

Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis

“…Recent data and comments about usage of peripheral vein as a route the for MSC Tx are conflicting. Eggenhofer et al (16) reported that in their experimental study, MSCs transplanted via the intravenous route were trapped in the capillary bed of the lungs and they did not migrate beyond. In contrast, in another study, rats with carbon tetrachloride-induced liver cirrhosis were transplanted with MSCs via 3 different routes: intravenous, intrahepatic, and intraperitoneal injections.…”