Elsevier

Biotechnology Advances

Volume 42, September–October 2020, 107338
Biotechnology Advances

Research review paper
Concise review: The challenges and opportunities of employing mesenchymal stromal cells in the treatment of acute pancreatitis

https://doi.org/10.1016/j.biotechadv.2019.01.005Get rights and content

Abstract

To date only small animal models have been employed to assess the effect of mesenchymal stromal cell (MSC) therapy on acute pancreatitis (AP), the most common cause of hospitalization for gastrointestinal diseases worldwide. We outline the challenges inherent in the small animal models of AP. We also point to specific benefits afforded by the adoption of larger animal models. The potential for MSC therapeutics in the treatment of AP was recognized over a decade ago. With sharper focus on the form of AP and development of new MSC delivery routes in larger animals, we believe the challenge can be engaged.

Section snippets

Acute pancreatitis

Acute pancreatitis (AP) is, by definition, the rapid onset of inflammation of the pancreas, and is the most common cause of hospitalization for gastrointestinal diseases worldwide (Peery et al., 2012). According the revised Atlanta Classification, there are two forms of the disease with different degrees of severity: acute necrotizing pancreatitis (severe) and interstitial edematous pancreatitis (mild) (Foster et al., 2016). Necrotizing pancreatitis accounts for 5–10% of all cases of acute

Mesenchymal stromal cells and autoimmune pancreatitis

AP presents in many forms but there is a current deficit in treatment options for all manifestations of AP. Recently, Kawakubo et al. (2018) reviewed 14 studies that had explored the use of mesenchymal stromal cells (MSCs) in small animal models of AP, since the first such report by Jung and colleagues in 2011b.

Thus, MSCs may represent a putative therapeutic for acute pancreatitis. Interestingly, in the 14 studies reviewed by Kawakubo et al. (ibid), none specified the form of AP being targeted

The challenges

The initial promising results, from small animal studies, on the beneficial effects of MSCs in models of AP have not yet been translated into human clinical trials. After the first such enciouraging report by Jung et al., 2011a, Jung et al., 2011b who transplanted clonal human MSCs into a rat model of edematous and necrotizing AP, Schneider and Saur (2011) reviewed the many issues still to be addressed including a better understanding of the cellular and molecular interactions between the

The opportunities

Although it is well established that mesenchymal stromal cells have the ability to differentiate into a variety of cell types, this is not the mechanism by which they attenuate the effects of acute pancreatitis. For example, Yang et al. (2013) observed beneficial effects from umbilical cord-derived MSC (UCMSCs) therapy on acute pancreatitis in rats within 24 h, a timeframe that precludes differentiation as a therapeutic mechanism. On the contrary, as has been discussed above, current

Future directions

Clearly, since MSCs have not been employed to our knowledge in large animal AP models, this represents the most important direction for future studies. However, as with much proposed cell therapy, this also raises the issue of the choice of cells to be employed. To be germane to translation to human therapy one would ideally employ human cells, but MSC cannot be xenotransplanted without invoking an immune response and immunosuppression would be contra-indicated. The alternative, using

Concluding remarks

The rescue of small animal AP models using MSCs shows that, at least for some causes of AP, MSC therapy may be a viable putative clinical approach. However, divergence has been shown between the effectiveness of, for example, the taurocholic acid model in small and large animal models and the latter have not been employed together with MSCs. Thus, a transition to large animal models, especially canine and porcine, is essential for future MSC studies. Such models provide the potential advantage

Conflict of interest

RRG and MKJ declare no conflicts of interest. JED is the founding president and officer of Tissue Regeneration Therapeutics Inc. (TRT), Toronto.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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    These authors contributed equally to the work.

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