Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: Potential for cell therapy in inflammatory bowel diseaseet

Giacomo Lanzoni, Francesco Alviano, Cosetta Marchionni, Laura Bonsi, Roberta Costa, Laura Foroni, Giulia Roda, Andrea Belluzzi, Alessandra Caponi, Francesca Ricci, Pier Luigi Tazzari, Pasqualepaolo Pagliaro, Roberta Rizzo, Francesco Lanza, Olavio Roberto Baricordi, Gianandrea Pasquinelli, Enrico Roda, Gian Paolo Bagnara

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background aims Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSC) are currently under evaluation in phase III clinical trials for inflammatory bowel disease and other intestinal disease manifestations. The therapeutic efficacy of these treatments may derive from a combination of the differentiation, trophic and immunomodulatory abilities of the transplanted cells. We investigated intestinal tissues as sources of MSC: such cells may support tissue-specific functions and hold advantages for engraftment and contribution in the gastrointestinal environment. Methods Intestinal specimens were collected, and the mucosa and submucosa mechanically separated and enzymatically digested. Mesenchymal stromal populations were isolated, expanded and characterized under conditions commonly used for MSC. The differentiation potential, trophic effect and immunomodulatory ability were investigated. Results We successfully isolated and extensively expanded populations showing the typical MSC profile: CD291, CD441, CD731, CD1051 and CD1661, and CD14 -, CD34- and CD45-. Intestinal mucosal (IM) MSC were also CD1171, while submucosal cultures (ISM MSC) showed CD341 subsets. The cells differentiated toward osteogenic, adipogenic and angiogenic commitments. Intestinal-derived MSC were able to induce differentiation and organization of intestinal epithelial cells (Caco-2) in three-dimensional collagen cultures. Immunomodulatory activity was evidenced in co-cultures with normal heterologous phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusions Multipotent MSC can be isolated from intestinal mucosal and submucosal tissues. IM MSC and ISM MSC are able to perform trophic and immunomodulatory functions. These findings could open a pathway for novel approaches to intestinal disease treatment.

Original languageEnglish (US)
Pages (from-to)1020-1031
Number of pages12
JournalCytotherapy
Volume11
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Cell therapy
  • Immunomodulation
  • Infl ammatory bowel disease
  • Intestinal stem cell
  • Mesenchymal stromal cells
  • Stem cells
  • Trophic function .

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

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