Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

Xiao, Juan; Yang, Rongbing; Biswas, Sanjib; Xin, Qin; Zhang, Min; Deng, Wenbin

doi:10.3390/ijms16059283

Cited by 58 publications

(46 citation statements)

References 85 publications

(107 reference statements)

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“…Some have even been tested on human OPCs derived from ES cells626364 but few of them have been tested on adult human OPCs, which may well behave differently, as spontaneous remyelination decreases with age65. There are just three published studies demonstrating the myelination capability of adult human OPCs transplanted into ex vivo and in vivo models666768.…”

Section: Discussionmentioning

confidence: 99%

Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis

Medina‐Rodriguez

Bribián

Boyd

et al. 2017

Sci Rep

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Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. The dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice. This combination of an advantageous effect on the immune response and an enhancement of repair, plus demonstration of its activity on adult human OPCs, leads us to propose dual PDE7-GSK3 inhibition, and specifically VP3.15, as a neuroprotective and neuroreparative disease-modifying treatment for MS.

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Section: Discussionmentioning

confidence: 99%

Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis

Medina‐Rodriguez

Bribián

Boyd

et al. 2017

Sci Rep

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“…IPSCs are probably now the more favoured cell vehicle for oligodendrocyte replacement, although the protocol for induction is inefficient, and concerns remain about genomic stability and the tumour risk associated with using these cells therapeutically. (12).…”

Section: Replacing Oligodendrocytesmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

2017

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Cell therapy is considered a promising potential treatment for multiple sclerosis, perhaps particularly for the progressive form of the disease for which there are currently no useful treatments. Over the past two decades or more, much progress has been made in understanding the biology of MS and in the experimental development of cell therapy for this disease. Three quite distinct forms of cell therapy are currently being pursued. The first seeks to use stem cells to replace damaged myelin-forming oligodendrocytes within the CNS; the second aims, in effect, to replace the individual's misfunctioning immune system, making use of haematopoietic stem cells; and the third seeks to utilise endogenous stem cell populations by mobilisation with or without in vitro expansion, exploiting their various reparative and neuroprotective properties. In this article we review progress in these three separate areas, summarising the experimental background and clinical progress thus far made.

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“…A large number of reported studies representing a wide spectrum of diseases reinforce this expectation. For example, MSC transplant has proven to be beneficial in preclinical as well as clinical studies of heart disease[92-105], renal disease[106-142], lung disease[143-159], liver disease[160-175], neural system disease[176-204], bone damage[205-227], skin wound healing[228-244], autoimmune disease[245-265], infectious diseases and sepsis[266-287], allergies and asthma[288-306], graft vs host disease[307-325] and diabetes[326]. …”

Section: Prospective Therapeutic Use Of Msc Transplantmentioning

confidence: 99%

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

Zorzopulos¹,

Opal²,

Hernando-Insúa³

et al. 2017

WJSC

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The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

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Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

Cited by 58 publications

References 85 publications

Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis

Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis

Cell Therapy for Multiple Sclerosis

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

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