Transplantation of Adipose-Derived Mesenchymal Stem Cells in Refractory Crohn’s Disease: Systematic Review

Abstract

Background:Crohn’s disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of adipose-derived mesenchymal stem cells. Aim:Systematic literature review to determine the different ways of adipose-derived mesenchymal stem cells administration in humans with luminal refractory and perianal fistulizing Crohn’s disease. Methods:It was conducted a search for articles (from 2008 to 2018) on PubMed and ScienceDirect databases using the keywords Crohn’s disease, fistulizing Crohn’s disease, luminal Crohn’s disease and transplantation of mesenchymal stem cells or mesenchymal stem cells or stromal cells. Thirteen publications were selected for analysis. Results:Only one study referred to the luminal Crohn´s disease. The number of cells administered was variable, occurring mainly through subcutaneous adipose tissue by liposuction. It could be highlighted the autologous transplant with exclusive infusion of mesenchymal stem cells. The procedures involved in pre-transplant were mainly curettage, setons placement and stitching with absorbable suture, and conducting tests and drug treatment for luminal Crohn´s disease. During transplant, the injection of mesenchymal stem cells across the fistula path during the transplant was mainly on the intestinal tract wall. Conclusion:Although the use of mesenchymal stem cells is promising, the transplant on the luminal region should be more investigated. The injection of mesenchymal stem cells, exclusively, is more explored when compared to treatment with other products. The preparation of the fistulizing tract and the location of cell transplantation involve standardized health care in most studies.

Current Overview on the Use of Mesenchymal Stem Cells for Perianal Fistula Treatment in Patients with Crohn’s Disease

“…Regarding CD, MSCs' ability to upregulate the CD4+ T cell subset is particularly important, as patients with CD are known to have a deficiency of those cells [9,10]. Furthermore, MSCs secrete various anti-inflammatory particles (including TGFB1, growth factors, interleukins and indoleamine 2,3-dioxygenase) and suppress M1 macrophages, cytotoxic T cells and dendritic cells [11].…”

“…Furthermore, they are known to have a higher replication rate and longer proliferation in culture [5,13]. They might also induce a stronger immunomodulatory effect, due to the fact they have higher secretion levels of cytokines, including TGFB1 and IL-6 [9].…”

Adipose Tissue-Derived Mesenchymal Stem Cells

“…ASCs have demonstrated the capacity to improve clinical symptoms and histologic disease activity in multiple studies of patients with severe IBD. Multiple clinical studies specifically included the patients’ refractory to antibiotics, immunomodulators, and surgical repair [ 34 , 35 ]. In this patient population, injection of ASCs around fistula enhanced the rate of fistula closure as assessed clinically and by MRI.…”

Fat Graft in Surgical Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)

“…These extracellular vesicles have been found to release miR-21, miR-181b, matrix metalloproteinases, milk fat globule EGF (MFG-E8), angiopoietin-like 1, and miR-375 to promote the neoangiogenesis during soft tissue healing and induce osteoblast differentiation and bone regeneration [47][48][49]. This expanded knowledge strongly promoted the initial enthusiasm in ASCs-based therapy, and during the following years, several investigations studied their clinical applicability to treat, among the others, osteoarthritis [50], Parkinson's disease [51], stroke [52,53], diabetic kidney disease [54], spinal cord injury [55], cutaneous scars [56], chronic skin wounds and soft tissues defects [57], burn wounds [58], alveolar ridge regeneration [59], Chron's disease [60], liver regeneration after partial hepatectomy [61], Graft-versus-Host disease [62], facial nerve regeneration [63], and intervertebral disc degeneration [64]. Nevertheless, it should be underlined that most of the initial expectations regarding the osteogenic properties of ASCs have been downsized by the following researchers, who demonstrated their limited differentiation potential toward osteogenic lineage [65].…”