Is This the Era of Interstitial Cells of Cajal Transplantation?

Park, Kyung Sik

doi:10.5056/jnm14064

Cited by 3 publications

(5 citation statements)

References 25 publications

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“…Firstly, cellular transplantation of ICC into the small intestine myenteric plexus of kit deficient mice restored the kit+ ICC MY networks and pacemaker activity [78]. Technically, this allotransplantation approach is feasible due to ICC capacity to undergo mitotic division, however, it might require transplantation of full-thickness muscle strips from other parts of the GI or from a matched donor, being thus currently not clinically feasible in patients [79]. Secondly, the potential of bone marrow-derived mesenchymal stem cells (MSCs) to differentiate into ICC and repopulate injured ICC networks in the murine small intestine is established [79].…”

Section: Future Prospectsmentioning

confidence: 99%

“…Technically, this allotransplantation approach is feasible due to ICC capacity to undergo mitotic division, however, it might require transplantation of full-thickness muscle strips from other parts of the GI or from a matched donor, being thus currently not clinically feasible in patients [79]. Secondly, the potential of bone marrow-derived mesenchymal stem cells (MSCs) to differentiate into ICC and repopulate injured ICC networks in the murine small intestine is established [79]. Following bone marrow transplantation (BMT), bone marrow-derived-ICC clusters were restored in the myenteric plexus of the irradiation injured small intestine of wild-type C57BL/6 mice [68, 80] and kit deficient mice, which normally lack ICC MY networks and pacemaker activity [81, 82].…”

Section: Future Prospectsmentioning

confidence: 99%

“…Following bone marrow transplantation (BMT), bone marrow-derived-ICC clusters were restored in the myenteric plexus of the irradiation injured small intestine of wild-type C57BL/6 mice [68, 80] and kit deficient mice, which normally lack ICC MY networks and pacemaker activity [81, 82]. This demonstrated that BM-derived kit+ cells are capable to migrate to and repopulate the ICC MY networks, although with conflicting outcomes on the recovery of motor activity in these studies, requiring further functional assessments [79].…”

Section: Future Prospectsmentioning

confidence: 99%

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Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal

Yadak

Breur

Bugiani

2019

Orphanet J Rare Dis

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BackgroundMNGIE is a rare and fatal disease in which absence of the enzyme thymidine phosphorylase induces systemic accumulation of thymidine and deoxyuridine and secondary mitochondrial DNA alterations. Gastrointestinal (GI) symptoms are frequently reported in MNGIE patients, however, they are not resolved with the current treatment interventions.Recently, our understanding of the GI pathology has increased, which rationalizes the pursuit of more targeted therapeutic strategies. In particular, interstitial cells of Cajal (ICC) play key roles in GI physiology and are involved in the pathogenesis of the GI dysmotility. However, understanding of the triggers of ICC deficits in MNGIE is lacking. Herein, we review the current knowledge about the pathology of GI dysmotility in MNGIE, discuss potential mechanisms in relation to ICC loss/dysfunction, remark on the limited contribution of the current treatments, and propose intervention strategies to overcome ICC deficits. Finally, we address the advances and new research avenues offered by organoids and tissue engineering technologies, and propose schemes to implement to further our understanding of the GI pathology and utility in regenerative and personalized medicine in MNGIE.ConclusionInterstitial cells of Cajal play key roles in the physiology of the gastrointestinal motility. Evaluation of their status in the GI dysmotility related to MNGIE would be valuable for diagnosis of MNGIE. Understanding the underlying pathological and molecular mechanisms affecting ICC is an asset for the development of targeted prevention and treatment strategies for the GI dysmotility related to MNGIE.

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Section: Future Prospectsmentioning

confidence: 99%

Section: Future Prospectsmentioning

confidence: 99%

Section: Future Prospectsmentioning

confidence: 99%

See 1 more Smart Citation

Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal

Yadak

Breur

Bugiani

2019

Orphanet J Rare Dis

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“…It is well established that ICC can trigger the spontaneous rhythmic contractions of smooth muscle in stomach. Thus, loss of ICCs and disruption to their networks are likely to play an important role in various gastrointestinal motility disorders in patients and animal models[ 11 ]. As a receptor tyrosine kinase, c-kit was used as a marker of ICC[ 19 ].…”

Section: Resultsmentioning

confidence: 99%

NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF

et al. 2016

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It is well known that natriuretic peptides (NPs) are involved in the regulation of gastrointestinal motility. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal motility and gastrointestinal dyskinesia is one of the important digestive tract symptoms of depression. However, it is unclear whether they are involved in depression-induced loss of ICC. The aim of the present study was to investigate the relationship between the natriuretic peptide signaling pathway and depression-induced loss of gastric ICC in depressed rats. These results showed that the expression of c-kit and stem cell factor (SCF) in smooth muscle layers of stomach were down-regulated in depressed rats at the mRNA and protein levels. The expression of natriuretic peptide receptor (NPR)-A, B and C were up-regulated in the stomach of depressed rats at the mRNA and protein levels. NPR-A, B and C can significantly decrease the expression of SCF to treat cultured gastric smooth muscle cells (GSMCs) obtained from normal rats with different concentrations of C-type natriuretic peptide (CNP). Pretreatment of cultured GSMCs with 8-Brom-cGMP (8-Br-cGMP, a membrane permeable cGMP analog), cANF (a specific NPR-C agonist) and CNP (10−6 mol/L) demonstrated that 8-Br-cGMP had a similar effect as CNP, but treatment with cANF did not. The results of the methyl thiazolyl tetrazolium bromide (MTT) assay indicated that high concentrations of cANF (10−6 mol/L) restrained the proliferation of cultured GSMCs. Taken together, these results indicate that the up-regulation of the NPs/NPR-C and NPs/NPR-A, B/cGMP signaling pathways may be involved in depression-induced loss of gastric ICC.

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“…However, no previous study has been performed with these cells on GP models. As ICCs arise from mesenchymal precursors [ 12 , 13 ], we envision that the MSCs can help regenerate the ICCs in gastric tissue, by directly differentiating into the latter [ 14 , 15 , 16 , 17 ], or by releasing paracrine factors that may help restore the depleted levels of ICCs [ 18 ]. Our pilot study, for the first time, will highlight the feasibility of delivering MSCs via a hydrogel scaffold to stomach tissues in vitro.…”

Section: Introductionmentioning

confidence: 99%

Delivery of Mesenchymal Stem Cells from Gelatin–Alginate Hydrogels to Stomach Lumen for Treatment of Gastroparesis

et al. 2018

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Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICCs) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric emptying. Regenerating these fundamental structures with mesenchymal stem cell (MSC) therapy would be helpful to restore gastric function in GP. MSCs have been successfully used in animal models of other gastrointestinal (GI) diseases, including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored whether mouse MSCs can be delivered from a hydrogel scaffold to the luminal surfaces of mice stomach explants. Mouse MSCs were seeded atop alginate–gelatin, coated with poly-l-lysine. These cell–gel constructs were placed atop stomach explants facing the luminal side. MSCs grew uniformly all across the gel surface within 48 h. When placed atop the lumen of the stomach, MSCs migrated from the gels to the tissues, as confirmed by positive staining with vimentin and N-cadherin. Thus, the feasibility of transplanting a cell–gel construct to deliver stem cells in the stomach wall was successfully shown in a mice stomach explant model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with cells and growth factors.

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Is This the Era of Interstitial Cells of Cajal Transplantation?

Cited by 3 publications

References 25 publications

Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal

Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal

NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF

Delivery of Mesenchymal Stem Cells from Gelatin–Alginate Hydrogels to Stomach Lumen for Treatment of Gastroparesis

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