Clinical Outcomes of Repeated Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells in Chronic Haemorrhagic Stroke. A One-Year Follow Up

Fauzi, Asra Al; Sumorejo, Purwati; Suroto, Nur Setiawan; Parenrengi, Muhammad Arifin; Wahyuhadi, Joni; Turchan, Agus; Mahyudin, Ferdiansyah; Suroto, Heri; Rantam, Fedik Abdul; Machfoed, Mochammad; Bajamal, Abdul Hafid; Lumenta, Christianto B.

doi:10.2174/1874205x01711010074

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…Practices for ICV device implantation were recommended, including: proper preoperative examination, prophylactic use of antibiotics 3 to 5 days in advance, establishment of a core team to perform the procedure, et cetera [70]. More importantly, clinical stem cell therapies using this administration route have been initiated in hemorrhagic stroke with noted safety and improved neurological outcomes [71,72]. The ICV delivery in stem cell therapy for brain injury after CA deserves more future exploration.…”

Section: Discussionmentioning

confidence: 99%

Intracerebroventricular Administration of hNSCs Improves Neurological Recovery after Cardiac Arrest in Rats

Wang

Lachance

et al. 2020

Stem Cell Rev and Rep

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Irreversible brain injury and neurological dysfunction induced by cardiac arrest (CA) have long been a clinical challenge due to lack of effective therapeutic interventions to reverse neuronal loss and prevent secondary reperfusion injury. The neuronal regenerative potential of neural stem cells (NSCs) provides a possible solution to this clinical deficit. We investigated the neuronal recovery potential of human neural stem cells (hNSCs) via intracerebroventricular (ICV) xenotransplantation after CA in rats and the effects of transplanted NSCs on the proliferation and migration of endogenous NSCs. Outcome measures included neurological functional recovery measured by neurological deficit score (NDS), electrophysiologic analysis of EEG, and assessment of proliferation and migration at the cellular level and the Wnt/β-catenin pathway at the molecular level. Neurological functional assessment based on aggregate neurological deficit score (NDS) showed better recovery of function after hNSCs therapy (P < 0.05). Tracking of stem cells' proliferation with Ki67 antibody suggested that the NSCs group had more prominent proliferation compared to control group (number of Ki67+ cells, Control VS. NSC: 89.0 ± 31.6 VS. 352.7 ± 97.3, P < 0.05). In addition, cell migration tracked by Dcx antibody showed more Dcx + cells migrated to the far distance zone from SVZ in the treatment group (P < 0.05). Further immunofluorescence staining confirmed that the expression of the Wnt signaling pathway protein (β-catenin) was upregulated in the NSC group (P < 0.05). ICV delivery of hNSCs promotes endogenous NSC proliferation and migration and ultimately enhances neuronal survival and neurological functional recovery. Wnt/β-catenin pathway may be involved in the initiation and maintenance of this enhancement.

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Section: Discussionmentioning

confidence: 99%

Intracerebroventricular Administration of hNSCs Improves Neurological Recovery after Cardiac Arrest in Rats

Wang

Lachance

et al. 2020

Stem Cell Rev and Rep

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“… 39 ICV administration of autologous BM-MSCs improved NIHSS from baseline in some haemorrhagic stroke patients ( Table 3 and Supplementary Table 1 ). 40 However, all these studies lack a control cohort which is crucial for determining efficacy.…”

Section: Intracerebroventricularand Intrathecal Transplantationmentioning

confidence: 99%

Editing a gateway for cell therapy across the blood–brain barrier

Buil

Tackenberg

Rust

2022

Brain

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Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for cell delivery to the injured brain. Local intracerebral injections are effective in precisely delivering cells into the stroke cavity but carry the risk of damaging adjacent healthy tissue. Systemic endovascular injections, meanwhile, are minimally invasive, but most injected cells do not cross central nervous system (CNS) barriers and become mechanically trapped in peripheral organs. Although the blood–brain barrier (BBB) and the blood–cerebro spinal fluid barrier (BCSFB) tightly limit the entrance of cells and molecules into the brain parenchyma, immune cells can cross these barriers especially under pathological conditions, such as stroke. Deciphering the cell surface signature and the molecular mechanisms underlying this pathophysiological process holds promise for improving the targeted delivery of systemic injected cells to the injured brain. In this review, we describe experimental approaches that have already been developed in which (a) cells are either engineered to express cell surface proteins mimicking infiltrating immune cells or (b) cell grafts are preconditioned with hypoxia or incubated with pharmacological agents or cytokines. Modified cell grafts can be complemented with strategies to temporarily increase the permeability of the blood–brain barrier. Although these approaches could significantly enhance homing of stem cells into the injured brain, cell entrapment in off-target organs remains a non-negligible risk. Recent developments in safety-switch systems, which enable the precise elimination of transplanted cells upon the administration of a drug, represent a promising strategy for selectively removing stem cells stuck in untargeted organs. In sum, the techniques described in this review hold great potential to substantially improve efficacy and safety of future cell therapies in stroke and may be relevant to other brain diseases.

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“…Intrathecally-administered UC-BSCs could migrate to the ischemic area and differentiate into neurons and astrocytes, which improved motor function in stroke rats [ 85 ]. Clinical applications of this method have supported the safety and potential efficacy, with improved neurological outcomes after intraventricular transplantation of BM-MSCs into patients with chronic sequelae of hemorrhagic stroke [ 86 , 87 ]. In cardiac arrest-induced global brain ischemia, human NSC infusion into the lateral ventricle 3 hours following resuscitation significantly improved neurological and electrophysiological outcomes of rats [ 88 ].…”

Section: Stem Cell Administration Routesmentioning

confidence: 99%

Optimizing Stem Cell Therapy after Ischemic Brain Injury

et al. 2020

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Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and <i>in vivo</i> potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.

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Clinical Outcomes of Repeated Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells in Chronic Haemorrhagic Stroke. A One-Year Follow Up

Cited by 9 publications

References 29 publications

Intracerebroventricular Administration of hNSCs Improves Neurological Recovery after Cardiac Arrest in Rats

Intracerebroventricular Administration of hNSCs Improves Neurological Recovery after Cardiac Arrest in Rats

Editing a gateway for cell therapy across the blood–brain barrier

Optimizing Stem Cell Therapy after Ischemic Brain Injury

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