title: Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging.
abstract: Multipotent mesenchymal stromal/stem cells (MSC) have shown potential clinical utility. However, previous assessments of MSC behavior in recipients have relied on visual detection in host tissue following sacrifice, failing to monitor in vivo MSC dispersion in a single animal and limiting the number of variables that can be observed concurrently. In this study, we used noninvasive, in vivo bioluminescent imaging to determine conditions under which MSC selectively engraft in sites of inflammation. MSC modified to express firefly luciferase (ffLuc-MSC) were injected into healthy mice or mice bearing inflammatory insults, and MSC localization was followed with bioluminescent imaging. The inflammatory insults investigated included cutaneous needle-stick and surgical incision wounds, as well as xenogeneic and syngeneic tumors. We also compared tumor models in which MSC were i.v. or i.p. delivered. Our results demonstrate that ffLuc-expressing human MSC (hMSC) systemically delivered to nontumor-bearing animals initially reside in the lungs, then egress to the liver and spleen, and decrease in signal over time. However, hMSC in wounded mice engraft and remain detectable only at injured sites. Similarly, in syngeneic and xenogeneic breast carcinoma-bearing mice, bioluminescent detection of systemically delivered MSC revealed persistent, specific colocalization with sites of tumor development. This pattern of tropism was also observed in an ovarian tumor model in which MSC were i.p. injected. In this study, we identified conditions under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time. Importantly, these consistent findings were independent of tumor type, immunocompetence, and route of MSC delivery.
authors: Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Shannon
authors: S
authors: Kidd
authors: Erika
authors: E
authors: Spaeth
authors: Jennifer L
authors: JL
authors: Dembinski
authors: Martin
authors: M
authors: Dietrich
authors: Keri
authors: K
authors: Watson
authors: Ann
authors: A
authors: Klopp
authors: Venkata Lokesh
authors: VL
authors: Battula
authors: Micheal
authors: M
authors: Weil
authors: Michael
authors: M
authors: Andreeff
authors: Frank C
authors: FC
authors: Marini
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008164:Luminescent Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D010051:Ovarian Neoplasms / Q000378:metabolism; D014781:Viscera / Q000166:cytology / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor; D008164:Luminescent Proteins