Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors

Watanabe, Shuhei; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hironari; Onodera, Kei; Nasuno, Masanao; Yamashita, Kentaro; Idogawa, Masashi; Naishiro, Yasuyoshi; Murata, Masaki; Adachi, Yasushi; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

doi:10.1007/s00535-013-0901-3

Cited by 66 publications

(64 citation statements)

References 56 publications

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“…Surprisingly, the therapeutic effects of MSCs do not depend on their full engraftment, but rely on the capacity of MSCs to inhibit pathogenic immune responses and to release trophic factors favoring tissue repair [55][56][57]. We found that the conditioned medium of MSCs including pleiotropic gut trophic factors promoted intestinal epithelial repair [58]. Consequently, we believe that discovery of the strategy to optimize MSC and ingredient analysis of MSC-conditioned medium (MSC-CM) would open new avenues for drug discovery and establish a basis for cell-based therapy for IBD (Fig.…”

Section: Msc and Ibdmentioning

confidence: 83%

Stem cell therapy for inflammatory bowel disease

2015

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Inflammatory bowel disease (IBD) could be curable by ''immune rest'' and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. The application of mesenchymal stem cells (MSCs) serving as a site-regulated ''drugstore'' is a recent concept, which suggests the possibility of an alternative treatment for many intractable diseases such as IBD. Depending on the required function of MSC, such as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized to maximize its therapeutic benefit. Therapeutic effects do not always require full engraftment of MSCs. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs, which favoring not only regulating immune responses but also promoting tissue repair, must directly enhance new drug discoveries for treatment of IBD. Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and patients. However, the translational arm of stem cell science remains in a relatively primitive state.Although several clinical studies using MSCs have been initiated, early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, and can be resolved only by scientifically unveiling the mechanisms of therapeutic action. In the present review, the authors outline how such information would facilitate the critical steps in the paradigm shift from basic research on stem cell biology to clinical practice of regenerative medicine for conquering IBD in the near future.

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Section: Msc and Ibdmentioning

confidence: 83%

Stem cell therapy for inflammatory bowel disease

2015

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“…Furthermore, MSC therapy was shown to suppress inflammation, apoptosis, and fibrosis in numerous disease models without MSC differentiation and engraftment in the injured tissue [5,16]. Therefore, clinical trials have shifted toward utilizing the biological functions of MSCs through trophic mechanisms and from local to systemic administration [17][18][19][20][21]. This is the main advantage of MSC therapy over embryonic stem (ES) cells and inducible pluripotent stem (iPS) cells, which require differentiation into specific cell lineages and engraftment in the target tissue; moreover, ES and iPS cells can form teratomas [22,23].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Mesenchymal stem cell therapy for acute and chronic pancreatitis

et al. 2017

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Mesenchymal stem cells (MSCs) have attracted attention as a cell source for regenerative medicine. In particular, MSCs have an anti-inflammatory effect by secreting several kinds of bioactive molecules. MSC therapy is now being applied to various gastrointestinal diseases, such as graft-versus-host disease, inflammatory bowel disease, and liver cirrhosis. Therefore, MSC therapy has the potential to be a novel treatment for acute and chronic pancreatitis by suppressing inflammation. Several studies have investigated the effect of MSC therapy on acute and chronic pancreatitis, but the underlying mechanisms remain unknown. In this review, we summarize the present status of MSC therapy for acute and chronic pancreatitis.

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“…We hypothesized that MSCs could be a potential cellular therapy because they express high levels of VEGF in culture relative to other growth factors and cytokines (33). We chose to use MSCs isolated from the colon in our studies because they have higher levels of VEGF expression as compared with MSCs isolated from the bone marrow (34).…”

Section: Acta2-creermentioning

confidence: 99%