Int J Stem Cells.  2018 Jun;11(1):39-47. 10.15283/ijsc17074.

Local Mesenchymal Stem Cell Therapy in Experimentally Induced Colitis in the Rat

• de la Portilla F
• Yuste Y
• Pereira S
• Olano C
• Maestre MV
• Padillo FJ

• KMID: 2413499
• DOI: http://doi.org/10.15283/ijsc17074

Abstract

BACKGROUND
Multipotent mesenchymal stem cells (MSCs) have been used in inflammatory bowel diseases because of their immunomodulatory and regenerative properties. We investigated their local use in an experimental model of colitis in the rat.
MATERIALS AND METHODS
Colitis was induced into 20 Wistar rats with local TNBS instillation. Allogeneic stem cells were derived from rat adipose tissue and labeled with PKH2 linker dye with creation of a control and a second group treated by a local injection into the rectal wall of 2×106 allogeneic adipose tissue-derived stem cells (ADSCs). The thicknesses of different components of the rectum were measured with comparisons made in different parts of the colon of the Hunter inflammatory score. PKH2-dyed ADSCs were detected by fluorescence microscopy.
RESULTS
AND CONCLUSIONS: Total colitis was induced in 19/20 rats with homing of fluorescent ADSCs. to the crypt base and perivascular space of the submucosa. There were no differences in component rectal wall thicknesses with a higher Hunter score in the treated group compared with the controls, in the rectum (3.8±2.74 vs. 1.5±2.37, respectively; p=0.017) and in right colon (2.5±1.08 vs. 0.20±0.42, respectively; p=0.0001). Local colonic injection of allogeneic adipose stem cells. in experimental colitis is feasible and safe. There is demonstrable homing of cells in chemically-induced colitis both to the treated region and parts of the colon distant to the MSC treatment site. Such cells readily proliferate in vitro and could potentially be a source for future treatment of resistant disease.

Keyword

Mesenchymal stem cells; Inflammatory bowel disease; Animal models; Colitis

MeSH Terms

Adipose Tissue
Animals
Colitis*
Colon
In Vitro Techniques
Inflammatory Bowel Diseases
Mesenchymal Stromal Cells*
Microscopy, Fluorescence
Models, Animal
Models, Theoretical
Rats*
Rats, Wistar
Rectum
Stem Cells

Figure

• 

  Fig. 1 Left image: Scheme of the treatment. The day of ADSCs injection and saline in the treated groups was defined as day 0. Right image: Body weight changes over time in both groups.

• 

  Fig. 2 Colonic immunofluorescence 10 days following TNBS-induced colitis treated by injection of 2×106 allogeneic adipose-derived mesenchymal stem cells. The cells have been marked with PKH26 (×40 magnification). Upper left image: Rectum; Upper right image: Descending colon; Lower left image: Transverse colon; Lower right image: Right colon.

• 

  Fig. 3 Comparative Hunter scoring of the different parts of the colon after TNBS-induced colitis (Control vs. ADSC-treated groups).

• 

  Fig. 4 Haematoxylin and eosin histology of the different colonic sections (Left: Control group; 1 rectum, 3 Descending colon, 5 Transverse colon, 7 Ascending colon - Right: ADSC-treated group; 2 rectum, 4 Descending colon, 6 Transverse colon, 8 Ascending colon). ×20 magnification.

Reference

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