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Localized colonic stem cell transplantation enhances tissue regeneration in murine colitis.

Zhou Q, Price DD, Dreher KL, Pronold B, Callam CS, Sharma J, Verne GN - J. Cell. Mol. Med. (2012)

Bottom Line: Adult stem cells have recently been used in various disease states to contribute wound-healing processes.Intra-colonic administration of CSCs is a potential therapeutic method for treating refractory symptoms in patients with chronic gastrointestinal diseases associated with chronic inflammation and visceral hypersensitivity.This method may be safer and should have far fewer side effects than systemic stem cell administration.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Texas Medical Branch, Galveston, TX 77555-0764, USA.

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Local stem cell transplantation reverses indicators of colitis: Changes seen in colonic pathology were graded using a validated histological injury score. Histology scores ranging from 0 to 15 were ascribed to each specimen. (A) Colon from an untreated IL-10−/− mouse. Colitis was severe with enterocyte loss, crypt inflammation, the presence in the lamina propria of mononuclear cells and neutrophils, and epithelial hyperplasia. In contrast, CSCs transplantation induced histological remission in IL-10−/− mice with active colitis. Approximately 16% of CSC-treated IL-10−/− mice (4 of 25) showed complete resolution (B); approximately 60% of CSC-treated IL-10−/− mice (15 of 25) had only a mild degree of inflammation (injury scores between 1 and 5) (C), and approximately 25% of CSC-treated IL-10−/− mice (6 of 25) showed only moderate inflammation (injury scores between 6 and 10) (D). (E) IL-10−/− mice exhibit a significant increase in their body weight after a single dose of local stem cell transplantation compared to the other groups.
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fig03: Local stem cell transplantation reverses indicators of colitis: Changes seen in colonic pathology were graded using a validated histological injury score. Histology scores ranging from 0 to 15 were ascribed to each specimen. (A) Colon from an untreated IL-10−/− mouse. Colitis was severe with enterocyte loss, crypt inflammation, the presence in the lamina propria of mononuclear cells and neutrophils, and epithelial hyperplasia. In contrast, CSCs transplantation induced histological remission in IL-10−/− mice with active colitis. Approximately 16% of CSC-treated IL-10−/− mice (4 of 25) showed complete resolution (B); approximately 60% of CSC-treated IL-10−/− mice (15 of 25) had only a mild degree of inflammation (injury scores between 1 and 5) (C), and approximately 25% of CSC-treated IL-10−/− mice (6 of 25) showed only moderate inflammation (injury scores between 6 and 10) (D). (E) IL-10−/− mice exhibit a significant increase in their body weight after a single dose of local stem cell transplantation compared to the other groups.

Mentions: Histopathology analysis was performed using an injury score [21-23] with scores ranging from 0 (none) to 15 (severe) 2 weeks after local CSCs infusion (Fig. 3A–D). We also performed histopathology analysis up to 28 days after CSCs colon transfusion (data not shown) and similar results were obtained as those at day 14. IL-10−/− mice develop spontaneous enterocolitis associated with weight loss, passage of mucous, rectal prolapse and diarrhoea. Histological analysis of colonic tissue from IL-10−/− mice without any treatment exhibited an injury score between 11 and 15. There was pancolitis without any skip areas in the colon (data not shown). There were no improvements in the histological score in IL-10−/− mice 2 weeks after local transplantation of CECs or vehicle transfusion (Fig. 3A). In contrast, localized intra-colonic transfusion of a single dose of CSCs induced histological remission in IL-10−/− mice with active colitis (Fig. 3B–D). Following a single dose of CSCs, 16% of IL-10−/− mice (4 of 25) fully recovered (Fig. 3B), 60% (15 of 25) had only a mild degree of inflammation remaining (Fig. 3C), and 25% (6 of 25) showed a moderate degree of colitis remaining (Fig. 3D). The mean ± standard deviation for the pathology scores were 12.57 ± 1.59 for the untreated IL-10−/− mice group, 12.80 ± 1.92 for the CEC-treated group and 3.88 ± 2.63 for the CSC-treated group. No evidence of colitis was detected in any wild-type mice. Local stem cell therapy ameliorated histological colitis throughout the colon as there were no significant differences between the histological scores of the proximal and distal sections of the colon in stem cell treated mice. In the mild inflammation group (Fig. 3C), may notice many inflammatory cells and increased epithelial heights which further supports that IL-10−/− mice is a good model to study chronic inflammation.


Localized colonic stem cell transplantation enhances tissue regeneration in murine colitis.

Zhou Q, Price DD, Dreher KL, Pronold B, Callam CS, Sharma J, Verne GN - J. Cell. Mol. Med. (2012)

Local stem cell transplantation reverses indicators of colitis: Changes seen in colonic pathology were graded using a validated histological injury score. Histology scores ranging from 0 to 15 were ascribed to each specimen. (A) Colon from an untreated IL-10−/− mouse. Colitis was severe with enterocyte loss, crypt inflammation, the presence in the lamina propria of mononuclear cells and neutrophils, and epithelial hyperplasia. In contrast, CSCs transplantation induced histological remission in IL-10−/− mice with active colitis. Approximately 16% of CSC-treated IL-10−/− mice (4 of 25) showed complete resolution (B); approximately 60% of CSC-treated IL-10−/− mice (15 of 25) had only a mild degree of inflammation (injury scores between 1 and 5) (C), and approximately 25% of CSC-treated IL-10−/− mice (6 of 25) showed only moderate inflammation (injury scores between 6 and 10) (D). (E) IL-10−/− mice exhibit a significant increase in their body weight after a single dose of local stem cell transplantation compared to the other groups.
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fig03: Local stem cell transplantation reverses indicators of colitis: Changes seen in colonic pathology were graded using a validated histological injury score. Histology scores ranging from 0 to 15 were ascribed to each specimen. (A) Colon from an untreated IL-10−/− mouse. Colitis was severe with enterocyte loss, crypt inflammation, the presence in the lamina propria of mononuclear cells and neutrophils, and epithelial hyperplasia. In contrast, CSCs transplantation induced histological remission in IL-10−/− mice with active colitis. Approximately 16% of CSC-treated IL-10−/− mice (4 of 25) showed complete resolution (B); approximately 60% of CSC-treated IL-10−/− mice (15 of 25) had only a mild degree of inflammation (injury scores between 1 and 5) (C), and approximately 25% of CSC-treated IL-10−/− mice (6 of 25) showed only moderate inflammation (injury scores between 6 and 10) (D). (E) IL-10−/− mice exhibit a significant increase in their body weight after a single dose of local stem cell transplantation compared to the other groups.
Mentions: Histopathology analysis was performed using an injury score [21-23] with scores ranging from 0 (none) to 15 (severe) 2 weeks after local CSCs infusion (Fig. 3A–D). We also performed histopathology analysis up to 28 days after CSCs colon transfusion (data not shown) and similar results were obtained as those at day 14. IL-10−/− mice develop spontaneous enterocolitis associated with weight loss, passage of mucous, rectal prolapse and diarrhoea. Histological analysis of colonic tissue from IL-10−/− mice without any treatment exhibited an injury score between 11 and 15. There was pancolitis without any skip areas in the colon (data not shown). There were no improvements in the histological score in IL-10−/− mice 2 weeks after local transplantation of CECs or vehicle transfusion (Fig. 3A). In contrast, localized intra-colonic transfusion of a single dose of CSCs induced histological remission in IL-10−/− mice with active colitis (Fig. 3B–D). Following a single dose of CSCs, 16% of IL-10−/− mice (4 of 25) fully recovered (Fig. 3B), 60% (15 of 25) had only a mild degree of inflammation remaining (Fig. 3C), and 25% (6 of 25) showed a moderate degree of colitis remaining (Fig. 3D). The mean ± standard deviation for the pathology scores were 12.57 ± 1.59 for the untreated IL-10−/− mice group, 12.80 ± 1.92 for the CEC-treated group and 3.88 ± 2.63 for the CSC-treated group. No evidence of colitis was detected in any wild-type mice. Local stem cell therapy ameliorated histological colitis throughout the colon as there were no significant differences between the histological scores of the proximal and distal sections of the colon in stem cell treated mice. In the mild inflammation group (Fig. 3C), may notice many inflammatory cells and increased epithelial heights which further supports that IL-10−/− mice is a good model to study chronic inflammation.

Bottom Line: Adult stem cells have recently been used in various disease states to contribute wound-healing processes.Intra-colonic administration of CSCs is a potential therapeutic method for treating refractory symptoms in patients with chronic gastrointestinal diseases associated with chronic inflammation and visceral hypersensitivity.This method may be safer and should have far fewer side effects than systemic stem cell administration.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Texas Medical Branch, Galveston, TX 77555-0764, USA.

Show MeSH
Related in: MedlinePlus