Page 11 - AN-4-3

Advanced Neurology Stem cell therapy in stroke treatment: Advances and prospects

a synergistic effect when administered following a stroke. the immunomodulatory abilities of MSCs are becoming
Stem cell transplantation is a potential new technique, more widely recognized. Several studies have studied
but it may also exacerbate existing comorbidities. the ability of MSCs in affecting both innate and adaptive
Several comorbid disorders associated with stroke have immune responses. 43,44 MSCs inhibit dendritic cell
been clinically described, and their incidence is rapidly differentiation and maturation by reducing the expression
increasing. Some of the clinically significant comorbid of co-stimulatory molecules and pro-inflammatory
33
conditions include diabetes and hypertension. cytokines, such as tumor necrosis factor-α (TNF-α) and
interleukin-12 (IL-12), while increasing the production
4.1.1. Stem cell therapy in diabetic stroke of anti-inflammatory cytokines, including transforming
Diabetes is a metabolic disorder, while stroke is a growth factor-β (TGF-β) and interleukin-10 (IL-10). This
cerebrovascular disease. However, diabetes-induced indirectly suppresses T-cell proliferation and contributes
vascular damage and an increased inflammatory milieu are to the healing process. 45,46 In addition, MSCs can directly
likely to contribute to poor post-stroke outcomes. Diabetic limit T-cell proliferation by inducing cell cycle arrest in
stroke patients have an increased pathogenic cascade, and all subsets, resulting in a quiescent state and decreased
interventions that benefit non-diabetic stroke patients may proliferation. In mice, MSC therapy not only modulates
not always be effective for diabetic stroke patients. As a inflammatory responses but also significantly lowers
34
result, there is a pressing need to develop stroke therapies dyslipidemia. 47,48 Given the critical role of inflammation
specifically for diabetics. Exosome therapy may be a better and immunomodulation in the onset and progression of
choice for diabetic stroke, with some preclinical studies atherosclerosis, MSC transplantation has been extensively
showing promising results. Stem cell-based therapy studied as a therapeutic approach to treat atherosclerosis
35
for stroke is a promising treatment approach with a long or hyperlipidemia-mediated stroke.
therapeutic window. These therapies enhance endogenous
central nervous system repair and neurorestorative 5. Recent advancements in stem cell
mechanisms, including angiogenesis, neurogenesis, therapy for stroke
vascular remodeling, and white matter remodeling. They 5.1. Different stem cell sources
also control inflammatory and immunological responses
both locally and systemically. 36 Stem cells can be isolated and cultured after being extracted
from the human body, and although they can hypothetically
4.1.2. Stem cell therapy in hyperlipidemia-induced be collected from any type of tissue, adipose tissue is a main
hypertensive stroke source of stem cells. As a therapy for neurodegenerative
diseases, the implementation of neuronal stem cells is
Atherosclerosis (AS) is the leading cause of cardiovascular evolving as a promising approach for reestablishing normal
and cerebrovascular disorders, with lipid buildup in the brain function. At present, a few types of stem cells are
49
vessel wall serving as the primary marker of AS. While available for mitigating the onset and progression of these
37
statins are currently used to reduce lipids and low-density diseases. BMSCs are most often utilized for treating
50
lipoprotein (LDL) levels in AS, the cure rate remains ischemic stroke, and several preclinical studies also support
low. As a result, there is an urgent need to develop new the efficacy of MSC transplantation as an alternative
therapeutic approaches, making stem cells a focus of therapeutic approach. MSCs are also intended to exert
extensive research. Stem cells are a type of cell that retain neuroprotective actions by secreting various neurotrophic
the ability to differentiate into various cell types and tissues. factors, such as brain-derived neurotrophic factor (BDNF),
Stem cell transplantation techniques have shown efficacy ciliary neurotrophic factor (CNTF), glial cell line-derived
in the treatment of other diseases. 38 neurotrophic factor (GDNF), vascular endothelial growth
The treatment for hyperlipidemia-induced factor (VEGF), platelet-derived growth factor (PDGF), and
hypertension with stem cells involves transplanting neutrophil-activating protein-2 (NAP-2), thereby promoting
healthy cells into damaged blood arteries, tissues, and neuronal cell differentiation. Umbilical cord MSCs are
51
organs. MSCs are the most effective option among all isolated from Wharton’s jelly and perivascular fluid of the
accessible cell types. MSCs are processed and cultured to umbilical cord and have shown superior differentiation
39
promote cell differentiation and treat diseases. They have potential, minimal immune rejection, and selective
been investigated as a promising therapeutic target for neuroprotective, neurogenic, and angiogenic properties. 52
various diseases, including myocardial infarction, acute
lung injury, acute renal failure, ischemia, and others, due to 5.2. Stem cell application method
their ability to differentiate into multiple cell lineages, such Stem cell number delivered to the target site and potential
as mesodermal and myogenic lineages. 37,40-42 Furthermore, side effects can be significantly influenced by the method

Volume 4 Issue 3 (2025) 5 doi: 10.36922/an.5582