Human mesenchymal stem cell therapy in the management of luminal and perianal fistulizing Crohn’s disease – review of pathomechanism and existing clinical data

ABSTRACT

Introduction: Crohn’s disease (CD) is a chronic, recurring, idiopathic disease which is associated with imbalanced mucosal immune response, manifesting as a chronic inflammation of any location throughout the gastrointestinal tract. The purpose of currently available therapy is to suppress the heightened immune response. However, these treatments have no direct influence on the healing process of damaged tissues. The mesenchymal stem cell (MSC) therapy may represent a new alternative solution in both luminal and fistulizing CD, as it is able to inhibit the inflammation and promote the regeneration process at the same time.

Areas covered: Aim of this review is to summarize the existing clinical data about the clinical impact of MSC therapy in luminal and perianal fistulizing CD.

Expert opinion: Clinical trials demonstrated that MSC transplantation has an outstanding, durable efficacy with low fistula recurrence in biological therapy-refractory fistulizing CD; however, further clinical trials are required to confirm its effectiveness in luminal CD. Unlike to biological therapy, MSCs are able to promote the regeneration process of damaged tissues as well. This additional benefit besides their sustained immunosuppressive effect with no decrease of efficiency over time makes MSCs a new, highly potential therapeutic approach in the management of inflammatory bowel disease.

KEYWORDS:

• Crohn’s disease
• mesenchymal stem cell
• fistula
• inflammatory bowel disease

Article highlights

• MSCs represent a heterogeneous group of multipotent, fibroblast-like plastic-adherent stem cells which could be identified in practically all vascularized tissues, but the cell concentration is highest in the adipose tissue, umbilical cord, and bone marrow.

• MSC transplantation represents a new alternative in the management of conventional or biological therapy-refractory luminal and fistulizing Crohn’s disease because it is able to inhibit the inflammation and directly promote the regeneration process.

• Previous studies reported high fistula closure rate using both autologous and allogeneic MSC transplantation.

• The allogeneic MSC transplantation does not require additional immunosuppressive therapy because MSCs do not elicit host immune response due to low expression of histocompatibility complexes (MHC) class I-II and co-stimulatory molecules (CD40, CD80, and CD86).

• Allogeneic MSC transplantation could be the best treatment choice because it provides opportunity for the mass production of standardized dosage MSC-containing formulations.

• Major limitations of autogenous MSC transplantation: expensive, two surgical interventions required, time-consuming expansion of stem cells, and non-standardized dose of cells.

• The disadvantage of MSC therapy compared with biological therapies is that the local administration of MSCs is an invasive procedure; however, contrary to other conventional surgical procedures, it does not increase the risk of injury of the anal sphincter.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer on this manuscript has disclosed that they have applied for 2 patents related to adipose-derived mesenchymal stem cells titled ‘Identification and isolation of multipotent cells from non-osteochondral mesenchymal tissue’ (WO 2006/057649) and ‘Use of adipose tissue-derived stromal stem cells in treating fistula’ (WO 2006/136,244).

Additional information

Funding

This paper was not funded