Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Abstract

Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

Pulsed focused ultrasound enhances the therapeutic effect of mesenchymal stromal cell-derived extracellular vesicles in acute kidney injury

“…Recently, there has been interest in the regenerative properties of mesenchymal stromal cell (MSC) therapy for the repair and regeneration of damaged kidney tissue [11,12]. MSCs are a heterogeneous population of cells found in various adult tissues.…”

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…There are various sources of MSCs, such as bone marrow, fat tissue, amniotic fluid, umbilical cord tissue, placental tissue, menstrual blood, salivary gland, Wharton jelly, dental pulp and pluripotent stem cells [ 10 , 11 ]. The therapeutic potential of MSCs is due to its differentiation into multiple cell lineages and regulation of immune responses via immunomodulation [ 12 ] MSCs can differentiate into epithelial, stromal, and endothelial cells, and have been shown to restore endometrial function and improve pregnancy outcomes [ 13 ]. Several studies have reported that MSC transplantation improves ovarian function and ovarian reserve, and this action may be mediated by paracrine signaling pathways [ 14 ].…”

Systemic administration of human umbilical cord‑derived mesenchymal stem cells effectively ameliorates the outcomes of a critically ill elderly patient with COVID‑19 with multiple comorbidities: A case report

“…Mesenchymal stem/stromal cells (MSCs) possess advantaged immunomodulatory and hematopoietic-supporting properties, together with a multi-lineage differentiation potential; they have been identified from numerous tissues and hold great promise for use in regenerative medicine (20)(21)(22)(23). Generally, the therapeutic effects of MSCs, include immunoregulation and tissue repair, mainly through direct-or trans-differentiation, in an autocrine and paracrine manner, as well as by supplying the microenvironment and homing methods (24)(25)(26)(27)(28). For decades, low-immunogenic MSCs have been shown to be safe and preferable for use in the management of recurrent and refractory diseases, such as spinal injury, type 2 diabetes, graft-vs.-host disease (GVHD), autoimmune diseases and hematological malignancies, as well as for severe influenza H5N1 caused by acute respiratory distress syndrome (ARDS) (20,24,(29)(30)(31).…”