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



            associated with live  cell  treatments, such  as  cancer  and   MSCs for transplantation, including the presence of
            immune rejections. Recent research indicates that these   markers such as CD29, CD44, CD73, CD90, and CD105,
            EVs can trigger endogenous repair processes in various   and the absence of markers such as CD34, CD45, CD14, and
            tissues, promote angiogenesis, and modulate inflammatory   human leukocyte antigen (HLA) class II. The cell number,
            responses. The targeting capabilities of modified EVs can   dosage, and route of administration are other important
            also  be  improved  by  customizing  them  to  carry  specific   factors to be considered in pre-clinical investigations.
            medicinal compounds. This adaptability makes stem   MSCs are transplanted using various methods, including
            cell-derived EVs attractive options for therapeutic use in   intravenous, intranasal, and intra-arterial delivery of 1 ×
            the treatment of various diseases, such as tissue damage,   10  – 8 × 10  cells.  Although transplanted MSCs have been
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            neurodegenerative disorders, and stroke. 64        shown to adapt to their new surroundings and differentiate
                                                               into  neurons,  astrocytes,  and  oligodendrocytes  following
            5.5. The use of 3D bioprocessing methods           intravenous and intranasal administration,  concerns
            Many attempts have been made to develop new 3D     remain regarding the impact on MSC migration in the
            bioprocesses that can accelerate the clinical application   brain. The ability of stem cell transplantation to achieve key
            of stem cell research. Apart from the numerous     therapeutic outcomes such as tissue regeneration, enhanced
            pharmacological and genetic preconditioning methods   angiogenesis, neovascularization, improved blood-brain
            already discussed, the biological characteristics of stem   barrier (BBB) function, and functional restoration remains
            cells can be improved by using 3D bioprocessing methods   controversial. More studies are needed to develop definitive
            that physically mimic the natural in vivo environment.    cell therapies for stroke.  The outcomes of stem cell therapy
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            Gradually, it is becoming evident that multiple passages   in stroke are discussed in Figure 3.
            during culture expansion utilizing traditional tissue
            culture flasks change the natural phenotype of MSCs. As   7. Clinical trial of stem cell therapy in stroke
            a result, MSC phenotypes and unique properties can be   patients
            effectively preserved by forming an MSC collection that   Stroke has become the leading cause of long-term
            mimics true 3D interactions between adjacent cells or the   disability, morbidity, and mortality, significantly reducing
            extracellular  matrix.  However,  techniques  for  growing   the quality of life. Neuroinflammation, a key component
            stem cells in 3D bioprocesses require further investigation.   of the pathophysiology of various forms of cerebrovascular
            While cells close to the outer layer remain viable, necrosis   diseases, is also associated with stroke. A  thorough
            occurs in the center of the cell mass due to the restricted   search of clinical trials on stroke uncovered 56 studies
            transport of nutrients, oxygen, and metabolic waste caused   investigating cerebrovascular stroke using regenerative
            by conventional static culture conditions. 66      medicine, including both autologous and allogeneic cell
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            6. Preclinical studies with stem cells in          therapies.  Most of these cells were obtained from bone
            stroke                                             marrow, adipose tissue, spinal cord, umbilical cord, and
                                                               mesenchymal tissue. An observer-blinded, open-label
            In recent years, increasing experimental proof has   clinical study was carried out to assess the long-term safety
            highlighted the potential of stem cells for stroke treatment.   and effectiveness of autologous MSCs. Following MSC
            Many types of stem cells are effective and safe at both pre-  transplantation, patients who received MSC treatment
            clinical and clinical levels for treating various neurological   showed clinical improvement, which was correlated with
            disorders. Preclinical approval of stem cells for stroke   both the degree of involvement of the subventricular area in
            treatment was significant. Numerous studies have evaluated   the lateral ventricle and blood levels of stromal cell-derived
            stem cells based on several parameters, including cell type,   factor 1 (SDF-1). The frequency of comorbidity was similar
            cell number, dosage, route of administration, safety, and   to that of control group.  A single-blind controlled Phase I/
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            efficacy. 67,68  MSCs are the most extensively researched   II study that included patients with middle cerebral artery
            and utilized stem cells for stroke management. Among   (MCA) stroke was conducted. At 5 – 9 days post-stroke,
            the tissue sources of MSCs, bone marrow and adipose   autologous  BM-MNCs  were  administered  as  a  therapy
            tissue are the most prevalent and well-researched, with   (Figure 4). An increase in plasma concentration of neural
            bone marrow being the earlies identified source.  Most   growth factor was observed, and no adverse effects were
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            preclinical studies have investigated various aspects of stem   reported during the 6-month follow-up, except for two
            cell transplantation for stroke using autologous BM-MSCs.   individuals who experienced partial seizures after 3 months.
            Other studies have documented the use of MSCs derived   According to the study’s findings, administering BM-MNCs
            from adipose tissue, umbilical cord, placenta, and other   intravenously is both beneficial and safe.  Patients with
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            sources. Surface marker profiling is utilized to characterize   MCA infarction participated in a randomized, single-

            Volume 4 Issue 3 (2025)                         7                                doi: 10.36922/an.5582
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