In clinical practise, most of experiences have been directed to treat anal fistula related with Crohn’s disease. In this context two routes of administration have been tried: intravenous (systemic) and intralesional.

Intravenous injection has been used by the Group sponsored by Osiris Therapeutics that, to the date, do not provide publications of the results (A Phase III, Multicenter, Placebo-controlled, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of PROCHYMAL[tm] Intravenous Infusion for the Induction of Remission in Subjects Experiencing Treatment-refractory Moderate-to-severe Crohn’s Disease. Responsible Party: Osiris Therapeutics. ClinicalTrials.gov Identifier: NCT00482092; http://​www.​clinicaltrials.​gov/​). They are using intravenous infusion of suspension of allogenic adult human MSCs, total of 1,200 million (high dose) or 600 million (low dose) cells infused in four visits over 2 weeks. These adult human stem cells are manufactured from healthy, volunteer donors, extensively tested, and are stored to be available as needed. According with the Osiris information, human and animal studies have shown that the cells do not require any donor–recipient matching. The cells may have both immunosuppressive and healing benefits in Crohn’s disease. The cells naturally migrate specifically to sites of inflammation, so their effects are believed to be local and self-limiting rather than systemic. Currently, they are enrolling subjects to evaluate the ability of PROCHYMAL to induce remission in subjects with moderate-to-severe disease (Crohn’s disease activity index—CDAI—of between 250 and 450, inclusive) who have failed or been intolerant of at least one drug in each of the steroid, immunosuppressant, and biologic classes (http://​www.​clinicaltrials.​gov/​). Although publications are not available is important to remark that this protocol is now running as a Phase III clinical trial (http://​www.​clinicaltrials.​gov/​).

The rest of the experiences using stem cells to treat fistulas have been designed using cells in intralesional way. One of them is using autologous MSCs from bone marrow [23] and the others from fat (autologous and allogenic) as we describe ahead (see Tables 18.1, 18.2, 18.3, and 18.4).