Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges

Abstract

Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is the leading cause of morbidity and mortality worldwide. Despite advances in pharmacological and surgical therapy, treatment for functional rehabilitation following stroke is limited with a consequent serious impact on quality of life. Over the past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as a novel strategy for various diseases including stroke due to their unique properties that include easy isolation, multipotent differentiation potential and strong paracrine capacity. Although MSCs have shown promising results in the treatment of stroke, there remain many challenges to overcome prior to their therapeutic application. In this review, we focus on the following issues: the scientific data from preclinical studies and clinical trials of MSCs in the treatment of stroke; the potential mechanisms underlying MSC-based therapy for stroke; the challenges related to the timing and delivery of MSCs and MSC senescence.

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest

“…Mesenchymal stem cells (MSCs), derived from bone marrow, placenta, adipose or other tissues, have been proven to be a promising therapy against regional cardiac and cerebral IR injury in diverse of studies ( Yan et al, 2019 ; Li et al, 2021 ). In the small-animal models of CA and resuscitation, MSCs administered before CA or after resuscitation have also shown its potent protection for post-resuscitation cardiac, cerebral dysfunction and injuries.…”

Recovery After Stroke: New Insight to Promote Brain Plasticity

“…Stem cells can secrete various trophic factors and key molecules, promote brain plasticity, and reduce overall inflammation. In particular, mesenchymal stem cells (MSCs) from bone marrow or adipose tissue have demonstrated efficacy in experimental animal stroke models (16)(17)(18)(19)(20)(21)(22)(23). These positive findings are translated to clinical trials, where MSCs and other cells (such as bone marrow mononuclear cells) have demonstrated safety in patients with stroke (24-30) and even efficacy in promoting improvement in white matter injuries at 1 year (31).…”

Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

“…Transplantation of different types of stem cells has the potential to develop into an effective method of stroke therapy [ 6 , 7 ]. Specifically, over the past two decades, multiple basic studies and clinical trials have demonstrated that transplantation of the mesenchymal stem cells (mesenchymal stromal cells, MSCs) is safe [ 8 ] and can promote recovery after stroke (reviewed in [ 9 , 10 ]). According to the International Society of Cell Therapy criteria, MSCs are defined as multipotent non-hematopoietic stem cells that are adherent to plastic and can differentiate into adipocytes, chondroblasts, osteoblasts, and myocytes in vitro.…”

“…To introduce transplantation of MSCs into clinical practice, it is necessary to understand the mechanisms of their therapeutic action better. Several mechanisms underlying the therapeutic effects of MSCs have been proposed, among them paracrine action, direct interaction with other cells, and substitution of dead/damaged parenchymal cells after homing inside the tissue and differentiation [ 9 , 16 ]. Paracrine action means secretion of factors inducing activation or modulation of activity of tissue stem/progenitor cells, stem cell niche cells, immune cells, epithelial cells, and perivascular cells.…”

“…MSCs secrete a wide range of different factors and extracellular vesicles that may have an important role in the regeneration of brain tissue and restoration of brain functioning [ 8 ]. Anti-inflammatory and immunomodulatory paracrine activities of MSCs are very well documented [ 9 , 26 ]. In addition, recent studies have demonstrated direct cell-to-cell interactions and the possibility of transfer of mitochondria and cytoplasm components from transplanted MSCs to host neural cells [ 27 , 28 ].…”