Stem Cells International

Stem Cells International / 2014 / Article
Special Issue

Mesenchymal Stem Cell Biodistribution, Migration, and Homing In Vivo

View this Special Issue

Editorial | Open Access

Volume 2014 |Article ID 292109 | 2 pages | https://doi.org/10.1155/2014/292109

Mesenchymal Stem Cell Biodistribution, Migration, and Homing In Vivo

Received06 Feb 2014
Accepted06 Feb 2014
Published11 Mar 2014

Mesenchymal stem cells (MSCs) were originally defined by their capacity to differentiate into various connective tissue lineages as well as support hematopoiesis in vitro via the production of various cytokines, chemokines, and adhesion molecules [1, 2]. During the past decade, MSCs have been shown to exhibit angiogenic, trophic, anti-inflammatory, and immunomodulatory activity using a variety of experimental paradigms [36]. Together with their easy availability and amenability to large-scale expansion ex vivo, these properties have propelled MSC-based therapies to the forefront of regenerative medicine and immune regulatory cell therapy. Currently, MSCs from a variety of tissue sources are being evaluated in over 200 clinical trials for the treatment of a diverse array of disease indications. Completed Phase I and II clinical trials have reported statistically significant benefits in patients with steroid-resistant graft versus host disease [7], severe systemic lupus erythematosus [8], complex perianal fistulas [9], and ischemic cardiomyopathy [10]. However, not all trials have met their primary endpoint of efficacy and while many factors contribute to suboptimal patient outcomes, key among them are the molecular mechanisms that govern MSC engraftment, homing, and biodistribution in vivo. Indeed, despite rapid progress in describing the therapeutic potency of MSCs in experimental animal models of disease, progress in understanding their biodistribution and mechanism of action in vivo has been slow to develop. For example, robust methodologies to track the fate of MSCs in vivo are critical toward establishing their tissue tropism, duration of engraftment, and rates of clearance. In addition, the identification of endogenous factors that function as chemoattractants and repellents also plays critical roles in directing transplanted cells to sites of tissue injury. Moreover, a clearer understanding of the signaling axes that regulate MSC trafficking in vivo would provide a means to direct cells to specific tissue and organs, thereby increasing overall efficacy of MSC-based therapies. The latter may also provide a means to mobilize endogenous MSCs and enhance their regenerative and immune regulatory properties. Finally, cellular crosstalk and cell-to-cell interactions also likely affect the biodistribution and survival of exogenously administered MSCs, but scant information exists regarding these processes in vivo. In fact, it is a subject of debate whether MSCs localize to tissue due to passive entrapment in small vessels, particularly in lung, or if cells employ active mechanisms similar to leukocytes to home to specific tissues. Therefore, continued study into the mechanism that regulates trafficking of endogenous and transplanted MSCs will shed novel insight into basic MSC biology and lead to the development of more potent cell-based therapies.

We hope that the readers of this special issue will find it highly informative. The papers contained within it address many of the aforementioned issues including methods to track MSCs in vivo, mechanisms that mediate MSC migration and homing including within the CNS, and novel delivery methods to target cells to specific organs. This piece of information will serve as a useful resource with respect to current limitations in the field and provide insights as to how to improve current methods to achieve more beneficial outcomes for MSC-based therapies.

Weian Zhao
Donald G. Phinney
Dominique Bonnet
Massimo Dominici
Mauro Krampera

References

  1. D. J. Prockop, “Marrow stromal cells as stem cells for nonhematopoietic tissues,” Science, vol. 276, no. 5309, pp. 71–74, 1997. View at: Publisher Site | Google Scholar
  2. T. M. Dexter, L. H. Coutinho, E. Spooncer et al., “Stromal cells in haemopoiesis,” Ciba Foundation Symposium, vol. 148, pp. 76–86, 1990. View at: Google Scholar
  3. S. Tomita, D. A. G. Mickle, R. D. Weisel et al., “Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation,” Journal of Thoracic and Cardiovascular Surgery, vol. 123, no. 6, pp. 1132–1140, 2002. View at: Publisher Site | Google Scholar
  4. L. A. Ortiz, M. Duteil, C. Fattman et al., “Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 26, pp. 11002–11007, 2007. View at: Publisher Site | Google Scholar
  5. A. Uccelli, L. Moretta, and V. Pistoia, “Mesenchymal stem cells in health and disease,” Nature Reviews Immunology, vol. 8, no. 9, pp. 726–736, 2008. View at: Publisher Site | Google Scholar
  6. A. I. Caplan and D. Correa, “The MSC: an injury drugstore,” Cell Stem Cell, vol. 9, no. 1, pp. 11–15, 2011. View at: Publisher Site | Google Scholar
  7. K. le Blanc, F. Frassoni, L. Ball et al., “Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study,” The Lancet, vol. 371, no. 9624, pp. 1579–1586, 2008. View at: Publisher Site | Google Scholar
  8. D. Wang, H. Zhang, J. Liang et al., “Allogeneic mesenchymal stem cell transplantation in severe refractory systemic lupus erythematosus: 4 years experience,” Cell Transplantation, 2013. View at: Google Scholar
  9. W. Y. Lee, K. J. Park, Y. B. Cho et al., “Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula,” Stem Cells, vol. 31, no. 11, pp. 2575–2581, 2013. View at: Publisher Site | Google Scholar
  10. J. M. Hare, J. E. Fishman, G. Gerstenblith et al., “Comparison of allogeneic vs. autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial,” The Journal of the American Medical Association, vol. 308, pp. 2369–2379, 2012. View at: Google Scholar

Copyright © 2014 Weian Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

2464 Views | 1225 Downloads | 20 Citations
 PDF  Download Citation  Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

We are committed to sharing findings related to COVID-19 as quickly and safely as possible. Any author submitting a COVID-19 paper should notify us at help@hindawi.com to ensure their research is fast-tracked and made available on a preprint server as soon as possible. We will be providing unlimited waivers of publication charges for accepted articles related to COVID-19. Sign up here as a reviewer to help fast-track new submissions.