Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.

The Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer – Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of the Use of Stromal Cell-Based Pharmacological Strategies

“…Mesenchymal stromal cells (MSCs) constitute a small population of multipotent, mobile cells, but an interesting one that has been intensively studied. MSCs participate in tissue homeostasis regulation homeostasis, tissue/organ repair, maintenance of blood vessel integrity and immune system modulation [40][41][42][43]. However, due the lack of MSC-specific markers and their phenotypic similarity to other stromal cells, it can be difficult to accurately characterise MSCs.…”

“…The chronic inflammation accompanying the tumour microenvironment is a key condition favouring the colonization of the TME by MSCs; indeed, numerous studies indicate that tumour-associated mesenchymal stromal cells can be recovered from various neoplastic tissues [38,47,48]. The main sources of MSCs are bone marrow, adipose tissue and dental pulp, but they can also be recovered from other organs, i.e., muscular, bone, and cartilage tissue in vivo; however, the most commonly-used tissue sources for obtaining MSCs are BM-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (A-MSCs) [40,[44][45][46]. It is postulated that MSCs are most often located near blood vessels, in permeating arterioles and within the tunica adventitia of arteries.…”

“…In addition to the mesodermal lineage, MSCs have high plasticity and be capable of transforming into cells of non-mesodermal origin i.e., ectodermal and endodermal lineages, such as neuronal cells, cardiomyocytes, hepatocytes, or epithelial cells. Further in vitro research of MSCs has allowed their identification based on other features, like the presence of a subset of other characteristic surface markers and the ability to form colonies [40,48,[52][53][54]. One set of markers proposed for the identification of MSCs includes the superficial proteins, for instance smooth muscle actin (SMA), Gremlin-1 (GREM1), Meflin (ISLR), PDPN (Podoplanin), STRO-1, and stage-specific embryonic antigen 4 (SSEA-4) [55][56][57][58][59][60][61].…”