Direct Evidence of Mesenchymal Stem Cell Tropism for Tumor and Wounding Microenvironments using In Vivo Bioluminescence Imaging
By Shannon Kidd, Erika L Spaeth, J. Dembinski, M. Dietrich, Keri Watson, A. Klopp, Lokesh Battula, M. Weil, Michael Andreeff, Frank C. Marini. Stem Cells, 2009
661 citations recorded by the source corpus.
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. STEM CELLS 2009;27:2614–2623
View Paper: https://www.semanticscholar.org/paper/ad0ef9c3fbb2eaad13ff845116e81139ee247d4a
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Citations in the corpus
- Accessories to the crime: functions of cells recruited to the tumor microenvironment. (2012, positive): “…et al., 2001; Psaila and Lyden, 2009), and (2) the myofibroblastic/MSC subtype of CAFs, likely also present in metastatic vascular stem cell niches (Kidd et al., 2009; Korkaya et al., 2011; Liu et al., 2011; Spaeth et al., 2008, 2009); similar niche-forming cells may also nurture CSCs inside…”
- Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs (2019, background): “The fate of these MSCs was further unveiled by demonstrating that MSCs become phagocytosed by blood-derived monocytes and neutrophils after their initial entrapment in the lungs and thereby become redistributed systemically with a major accumulation in the liver and the spleen (31, 87) (Figure 1B).”
- Targeting cancer stem cell pathways for cancer therapy (2020, background): “494, 495 MSCs are considered to be an ideal vector for gene therapy because of their characteristics of homing to and secreting cytokines in tumors.”