Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice

Kim, Heejaung; Kim, Ho; Choi, Mi Ran; Hwang, Se Jin; Nam, Ki-Hoan; Kim, Hyoung-Chin; Han, Jin Soo; Kim, Kyung Suk; Yoon, Hyun Soo; Kim, Seung H.

doi:10.1016/j.neulet.2009.10.074

Cited by 129 publications

(99 citation statements)

References 23 publications

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“…Clinically, however there are no options; no drug has been able to stop or even delay ALS progression. For this reason, stem cell transplantation has emerged as a distinctive strategy to replace ALS affl icted motor neurons and glial cells (Kim et al, 2010;Lepore et al, 2008) . Indeed, it has been possible to diff erentiate stem cells into either motor neurons or glial cells in vitro (Dimos et al, 2008;Karumbayaram et al, 2009;Song et al, 2011).…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Nualart¹,

Salazar²,

Oyarce³

et al. 2012

Biol. Res.

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Stem cells are considered a valuable cellular resource for tissue replacement therapies in most brain disorders. Stem cells have the ability to self-replicate and diff erentiate into numerous cell types, including neurons, oligodendrocytes and astrocytes. As a result, stem cells have been considered the "holy grail" of modern medical neuroscience. Despite their tremendous therapeutic potential, little is known about the mechanisms that regulate their diff erentiation. In this review, we analyze stem cells in embryonic and adult brains, and illustrate the diff erentiation pathways that give origin to most brain cells. We also evaluate the emergent role of the well known anti-oxidant, vitamin C, in stem cell diff erentiation. We believe that a complete understanding of all molecular players, including vitamin C, in stem cell diff erentiation will positively impact on the use of stem cell transplantation for neurodegenerative diseases.

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Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Nualart¹,

Salazar²,

Oyarce³

et al. 2012

Biol. Res.

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“…Cell dosage is a primary parameter for clinical cell therapy and in the case of bone marrow-derived mononuclear cell treatment for patients with critical limb ischemia (CLI) condition, the dose range is ∼0.3 ∼ 2 × 10 9 cells (8). There are several reports to investigate the effects of cell dosage on therapeutic outcomes in animal models (9,10). For instance, injection of 3 × 10 5 MSCs exhibited no significant therapeutic angiogenesis in a mouse ischemic limb model compared with 1 × 10 6 MSCs, which was shown to be the minimum dosage with therapeutic effects (11).…”

mentioning

confidence: 99%

Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

134

143

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The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell-cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 10 5 hMSCs realized better ischemic limb salvage than treatment with 10 6 freeinjected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy.C ell-based regenerative therapy holds great promise for repair and restoration of damaged tissues or organs with numerous clinical trials and preclinical animal testing reported for treating complex diseases (1). Common route of cell administration for clinical cell therapy is based on either systematic administration (e.g., i.v. infusion), relying on cells homing to the lesion sites (2), or direct injection of cells into the damaged tissues (3). However, therapeutic benefits of the administered cells are still limited and sometimes irreproducible due to cell loss and cell death (4). Taking cell therapy for ischemic heart diseases as an example, only ∼5% of mesenchymal stem cells (MSCs) survived after being transplanted into an infarcted porcine heart (5). Mechanical damage during injection, high rate of cell loss and leakage to surrounding tissues, cell death due to lack of appropriate cell-cell and cell-matrix interactions in the ischemic and inflammatory lesion tissues could all contribute to poor cell retention, survival, functionality, and reproducibility of the treatment (6, 7).A rational solution to enhance the therapeutic efficacy and reproducibility of cell therapy is to administer a large dose of cells to ensure sufficient number of functional cells ...

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“…Stem cell therapies may modify disease pathophysiology [11], slow down or halt the progression of disease, and even improve neuromuscular function and motor unit pathology, possibly by providing protective factors to surrounding cells, modulating the host immune environment, inhibiting inflammation, or even replacing injured cells [12][13][14][15][16][17]. For patients carrying genetic mutations related to ALS, genetic corrected stem cells could be generated to correct the mutation, and for those carrying no genetic mutation, the protective and replacing effect of allogeneic stem cells are available.…”

Section: Resultsmentioning

confidence: 99%

“…When locally or systemically transplanted, stem cells are capable of migrating to disease-associated loci to exert the desired therapeutic effect [10]. Currently available cell therapies may take advantage of a variety of stem cells to modify disease pathophysiology [11], slow down or even halt the progression of disease, possibly by providing protective factors to surrounding cells, modulating the host immune environment, inhibiting inflammation, or even replacing injured cells [12][13][14][15][16][17]. Several types of stem cells have been studied as possibilities for treating ALS, including neural stem cells (NSCs), mesenchymal stem cells (MSCs), glial-restricted progenitor cells (GRPs), embryonic stem cells (ESCs), and induced pluripotent stem cells (IPSCs) [18].…”

Section: Introductionmentioning

confidence: 99%

Stem Cell Therapy for Amyotrophic Lateral Sclerosis

Chen

Feldman

2017

Molecular and Cellular Therapies for Motor Neuron Diseases

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Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice

Cited by 129 publications

References 23 publications

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia

Stem Cell Therapy for Amyotrophic Lateral Sclerosis

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