Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model

Liu, L; Chiu, Philip Wai Yan; Lam, P. M.; Poon, Chi‐Sang; Lam, Candice C.; Ng, Enders Kwok Wai; Lai, Paul

doi:10.1002/bjs.9724

Cited by 50 publications

(37 citation statements)

References 26 publications

(31 reference statements)

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“…Intestinal repair is a complex process that involves stromal-epithelial cell communication to restore the integrity of the bowel wall. Myofibroblasts are stromal cells of the gastrointestinal (GI) tract that are a known target of inflammatory mediator signaling [1–4] and appear to play an important role in restoring intestinal homeostasis [5–7] Myofibroblasts migrate to areas of injury, and interact with the overlying epithelium to regulate cell proliferation as well as deposition and remodeling of the underlying extracellular matrix [6, 8–11]. …”

Section: Introductionmentioning

confidence: 99%

Bradykinin stimulates protein kinase D–mediated colonic myofibroblast migration via cyclooxygenase-2 and heat shock protein 27

Chu

Saini

Liu

et al. 2017

Journal of Surgical Research

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Background Inflammatory bowel disease (IBD) is characterized by episodic intestinal injury and repair. Myofibroblasts are gastrointestinal (GI) tract stromal cells that regulate the reparative process, and are known targets of inflammatory mediators including bradykinin (BK). However, the mechanisms through which inflammation regulates myofibroblast-induced wound healing remain incompletely understood. Here, we demonstrate, for the first time, that BK stimulates myofibroblast migration through protein kinase D (PKD)-mediated activation of the COX-2 and Hsp27 pathways. Materials and Methods CCD-18Co is a human colonic myofibroblast cell line used from passages 8–14. An in vitro scratch assay assessed the effect of BK (100nM) on myofibroblast migration over 24h in the presence or absence of several inhibitors (CID755673 (10 µM) and NS398 (10 µM)). Hsp27 siRNA evaluated the effect of Hsp27 on colonic myofibroblast migration. Antibodies to pPKD, pHsp27, and COX-2 evaluated expression levels by Western blot. Results BK stimulated myofibroblast migration over 24h. BK also led to rapid and sustained phosphorylation of PKD at Ser-916, rapid phosphorylation of Hsp27 at Ser-82, and increased COX-2 expression over 4h. BK-mediated COX-2 expression and Hsp27 phosphorylation were both inhibited by the PKD inhibitor CID755673. Similarly, BK-induced myofibroblast migration was significantly inhibited by CID755673 (p<0.05), by the direct COX-2 inhibitor NS398 (p<0.05), and by Hsp27 siRNA (p<0.05). Conclusions BK stimulates myofibroblast migration through PKD-mediated activation of COX-2 and Hsp27. PKD, COX-2 and Hsp27 all appear to regulate myofibroblast cell migration, a stromal population that may play an important role in mucosal healing in the setting of inflammation.

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Section: Introductionmentioning

confidence: 99%

Bradykinin stimulates protein kinase D–mediated colonic myofibroblast migration via cyclooxygenase-2 and heat shock protein 27

Chu

Saini

Liu

et al. 2017

Journal of Surgical Research

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“…Enhanced healing of gastric perforation by PEI/PAA powder treatment. To further demonstrate that the PEI/PAA powder can be used as sealants to treat gastrointestinal perforation, we used an in-vivo rat gastric perforation model [42][43][44] (Fig. 5a).…”

Section: Resultsmentioning

confidence: 99%

Ultra-fast self-gelling powder mediate robust wet adhesion to promote healing of gastrointestinal perforations

Peng

Xia

et al. 2020

Preprint

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Achieving strong adhesion of bioadhesives on wet tissues remains a challenge and an acute clinical need due to the interfering interfacial water and lack of adhesive–tissue interactions. Herein we report a self-gelling and adhesive polyethyleneimine and polyacrylic acid (PEI/PAA) powder, which can absorb interfacial water to rapidly form a physically crosslinked hydrogel in situ within two seconds due to strong physical interactions between the polymers. Furthermore, the physically crosslinked polymers can diffuse into the substrate polymeric network to enhance wet adhesion on various tissues. Superficial deposition of PEI/PAA powder can effectively seal damaged porcine stomach and intestine despite excessive mechanical challenges. We further demonstrate the use of PEI/PAA powder as sealants to enhance the treatment outcomes of gastric perforation in a rat model. Owing to their strong wet adhesion, excellent cytocompatibility, adaptability to fit complex target sites, and easy synthesis, we believe that the PEI/PAA powder are promising bioadhesives with a wide array of biomedical applications.

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“…Several studies have demonstrated the ability of MSCs to preferentially migrate to sites of injury when infused in animal models (27–29). After receiving appropriate signals during tissue inflammation, MSCs could migrate to the lesions of the colon where they assisted in recovery, displaying high therapeutic potential with regards to tissue repair and/or the control of local inflammation (30). The expression of growth factors, cytokines and extracellular matrix receptors by MSCs may drive this process (31,32).…”

Section: Discussionmentioning

confidence: 99%

Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis

Hu¹,

Zhao²,

Zhang³

et al. 2016

Experimental and Therapeutic Medicine

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One of the primary targets of the clinical treatment of ulcerative colitis (UC) is to repair the damaged colonic mucosa. Mesenchymal stem cells (MSCs) have therapeutic potential in regenerative medicine due to their differentiation capacity and their secretion of numerous bioactive molecules. The present study describes a clinical trial (trial registration no. NCT01221428) investigating the safety and therapeutic effect of MSCs derived from human umbilical cord on moderate to severe UC. Thirty-four patients with UC were included in group I and treated with MSC infusion in addition to the base treatment, and thirty-six patients were in group II and treated with normal saline in addition to the base treatment. One month after therapy, 30/36 patients in group I showed good response, and diffuse and deep ulcer formation and severe inflammatory mucosa were improved markedly. During the follow up, the median Mayo score and histology score in group I were decreased while IBDQ scores were significantly improved compared with before treatment and group II (P<0.05). Compared with group II, there were no evident adverse reactions after MSC infusion in any of the patients in group I, and no chronic side effects or lingering effects appeared during the follow-up period. In conclusion, MSC infusion might be a useful and safe therapy for treating UC.

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Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model

Cited by 50 publications

References 26 publications

Bradykinin stimulates protein kinase D–mediated colonic myofibroblast migration via cyclooxygenase-2 and heat shock protein 27

Bradykinin stimulates protein kinase D–mediated colonic myofibroblast migration via cyclooxygenase-2 and heat shock protein 27

Ultra-fast self-gelling powder mediate robust wet adhesion to promote healing of gastrointestinal perforations

Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis

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