Intrathecal cell therapy with autologous stromal cells increases cerebral glucose metabolism and can offer a new approach to the treatment of Alzheimer's type dementia

Vaquero, Jesús; Zurita, Mercedes; Mucientes, Jorge; Pascual, Mario; Fernández-Mateos, Cecilia; García, Estefanía; Fernández-Guinea, Sara

doi:10.1016/j.jcyt.2019.02.009

Cited by 12 publications

(5 citation statements)

References 21 publications

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“…Therefore, it is tough to firmly say what kinds of cell types are effective or not. Recently, most clinical cell therapies conducted for several neurological diseases or damage, including AD has reported neurorestorative effects [18][19][20][21][22]. Each cell type should have a reasonable indication, appropriate transplanting routes, optimized doses, and appropriate therapeutic time windows.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of clinical cell therapies in Alzheimer’s disease

Guo¹,

Wang²,

Li³

et al. 2021

Journal of Neurorestoratology

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Alzheimer’s disease (AD) is a neurodegenerative disease dominated by progressive cognitive dysfunction causing significant social, economic, and medical crises. Cell therapy has demonstrated favorable effects for AD. This pilot study examined the safety and neurorestorative effects of the olfactory ensheathing cell (OEC), olfactory neuron (ON), and Schwann cell (SC) on patients with AD. Seven patients with AD were enrolled in this two-center, randomized, double-blind, and placebo- controlled cell therapy study with a subsequent 12-month follow-up. We randomly assigned one or two participants in OEC, ON, and SC therapy or OEC combined with ON and placebo control. All enrolled patients were injected cells or medium into the olfactory sub-mucosa. They got an assessment of Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating before treatment and 1, 3, 6, 12 months after treatment. We performed MRI or CT scans before treatment and 12 months after treatment. After integrating the results from the three evaluation methods, all cell types showed better results than a placebo control. ON and SC seem to exhibit more vital potential neurorestorative ability to enhance or convert the neurological functions of patients with AD, and OEC may help AD patients keep neurological functions stable. In this pilot study, there was no adverse or side-effect event. The results of this study strongly suggest conducting a phase II clinical trial of ON, SC, and OEC therapy to prove their neurorestorative effect on patients with AD.

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Section: Discussionmentioning

confidence: 99%

A pilot study of clinical cell therapies in Alzheimer’s disease

Guo¹,

Wang²,

Li³

et al. 2021

Journal of Neurorestoratology

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“…Third, the migration of MSCs in the rat brain was not followed up after 12 h. From this study, what can be said is that the minimum time required for MSCs to migrate to the brain is around 12 h. Fourth, the therapeutic efficacy of MSCs delivered via the intrathecal route was not evaluated. Although we did not evaluate the therapeutic efficacy of MSCs because the experimental animals we used were healthy, there are many reports in which intrathecally delivered MSCs have shown positive clinical outcomes [42,43].…”

Section: Discussionmentioning

confidence: 99%

Intrathecal Injection in a Rat Model: A Potential Route to Deliver Human Wharton’s Jelly-Derived Mesenchymal Stem Cells into the Brain

Kim

Lee

et al. 2020

IJMS

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Mesenchymal stem cells (MSCs) are considered as promising therapeutic agents for neurodegenerative disorders because they can reduce underlying pathology and also repair damaged tissues. Regarding the delivery of MSCs into the brain, intravenous and intra-arterial routes may be less feasible than intraparenchymal and intracerebroventricular routes due to the blood–brain barrier. Compared to the intraparenchymal or intracerebroventricular routes, however, the intrathecal route may have advantages: this route can deliver MSCs throughout the entire neuraxis and it is less invasive since brain surgery is not required. The objective of this study was to investigate the distribution of human Wharton’s jelly-derived MSCs (WJ-MSCs) injected via the intrathecal route in a rat model. WJ-MSCs (1 × 106) were intrathecally injected via the L2-3 intervertebral space in 6-week-old Sprague Dawley rats. These rats were then sacrificed at varying time points: 0, 6, and 12 h following injection. At 12 h, a significant number of MSCs were detected in the brain but not in other organs. Furthermore, with a 10-fold higher dose of WJ-MSCs, there was a substantial increase in the number of cells migrating to the brain. These results suggest that the intrathecal route can be a promising route for the performance of stem cell therapy for CNS diseases.

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“…Safety, survival and tolerability goals were met for all primary and secondary endpoints [ 166 ]. In addition, a case study using intrathecal injection of autologous MSCs demonstrated significant improvement in clinical symptoms in two patients and overall glucose metabolism in the brain as determined by 18F-fluorodeoxyglucose PET imaging [ 167 ]. These effective paradigms imply that MSCs have a minimal risk of side effects and are suitable for widespread usage in upcoming AD clinical trials.…”

Section: Overview Of Alzheimer’s Diseasementioning

confidence: 99%

Potential use of iPSCs for disease modeling, drug screening, and cell-based therapy for Alzheimer’s disease

Marei,

Khan,

Hasan

2023

Cell Mol Biol Lett

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Alzheimer’s disease (AD) is a chronic illness marked by increasing cognitive decline and nervous system deterioration. At this time, there is no known medication that will stop the course of Alzheimer’s disease; instead, most symptoms are treated. Clinical trial failure rates for new drugs remain high, highlighting the urgent need for improved AD modeling for improving understanding of the underlying pathophysiology of disease and improving drug development. The development of induced pluripotent stem cells (iPSCs) has made it possible to model neurological diseases like AD, giving access to an infinite number of patient-derived cells capable of differentiating neuronal fates. This advance will accelerate Alzheimer’s disease research and provide an opportunity to create more accurate patient-specific models of Alzheimer’s disease to support pathophysiological research, drug development, and the potential application of stem cell-based therapeutics. This review article provides a complete summary of research done to date on the potential use of iPSCs from AD patients for disease modeling, drug discovery, and cell-based therapeutics. Current technological developments in AD research including 3D modeling, genome editing, gene therapy for AD, and research on familial (FAD) and sporadic (SAD) forms of the disease are discussed. Finally, we outline the issues that need to be elucidated and future directions for iPSC modeling in AD.

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Intrathecal cell therapy with autologous stromal cells increases cerebral glucose metabolism and can offer a new approach to the treatment of Alzheimer's type dementia

Cited by 12 publications

References 21 publications

A pilot study of clinical cell therapies in Alzheimer’s disease

A pilot study of clinical cell therapies in Alzheimer’s disease

Intrathecal Injection in a Rat Model: A Potential Route to Deliver Human Wharton’s Jelly-Derived Mesenchymal Stem Cells into the Brain

Potential use of iPSCs for disease modeling, drug screening, and cell-based therapy for Alzheimer’s disease

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