ADSC Therapy in Neurodegenerative Disorders

Chan, Tzu Min; Chen, Julia Yi Ru; Ho, Ling‐Jun; Lin, Hui; Hsueh, Kuo Wei; Liu, Demeral David; Chen, Yi Hung; Hsieh, An Cheng; Tsai, Nu‐Man; Hueng, Dueng‐Yuan; Tsai, Sheng Tzeng; Chou, Pei Wen; Lin, Shinn Zong; Harn, Horng Jyh

doi:10.3727/096368914x678445

Cited by 53 publications

(42 citation statements)

References 87 publications

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“…In ischemic, neurodegenerative and traumatic pain, their beneficial effect seems to be dependent on their modulatory and stimulating properties of mechanisms involved in tissue repair (Chan et al, 2014). In several anatomical localized neuropathic pain models (chronic constriction injury (Franchi et al, 2012); spared nerve injury (Siniscalco et al, 2011; spinal cord injury (Watanabe et al, 2015)), the administration of stem cells by i.v.…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation

et al. 2018

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Keywords:Adipose stem cells Chemotherapy-induced neuropathic pain VEGF-A VEGF 165 b Bevacizumab VEGF-R1 Intrathecal TGF-b1 EGF a b s t r a c t Oxaliplatin therapy of colorectal cancer induces a dose-dependent neuropathic syndrome in 50% of patients. Pharmacological treatments may offer limited relief; scientific efforts are needed for new therapeutic approaches. Therefore we evaluated in a preclinical setting the pain relieving properties of mesenchymal stem cells and its secretome. Rat adipose stem cells (rASCs) were administered in a rat model of oxaliplatin-induced neuropathy.A single intravenous injection of rASCs reduced oxaliplatin-dependent mechanical hypersensitivity to noxious and non-noxious stimuli taking effect 1 h after administration, peaking 6 h thereafter and lasting 5 days. Cell-conditioned medium was ineffective. Repeated rASCs injections every 5 days relieved pain each time with a comparable effect. Labeled rASCs were detected in the bloodstream 1 and 3 h after administration and found in the liver 24 h thereafter. In oxaliplatin-treated rats, the plasma concentration of vascular endothelial growth factor (pan VEGF-A) was increased while the isoform VEGF 165 b was upregulated in the spinal cord. Both alterations were reverted by rASCs. The anti-VEGF-A monoclonal antibody bevacizumab (intraperitoneally) reduced oxaliplatin-dependent pain. Studying the peripheral and central role of VEGF 165 b in pain, we determined that the intraplantar and intrathecal injection of the growth factor induced a pro-algesic effect. In the oxaliplatin neuropathy model, the intrathecal infusion of bevacizumab, anti-rat VEGF 165 b antibody and rASCs reduced pain.Adult adipose mesenchymal stem cells could represent a novel approach in the treatment of neuropathic pain. The regulation of VEGF-A is suggested as an effective mechanism in the complex response orchestrated by stem cells against neuropathy.

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Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation

et al. 2018

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“…Studies on ADSCs have provided evidence for restoration of damaged chondrocytes and injured cartilage (15). In addition, ADSCs have also been indicated to suppress inflammation, promote angiogenesis and enhance fibroblast proliferation (5,26). Human ADSCs isolated by using minimally invasive procedures could illustrate tremendous potential in tissue repair and tissue regeneration applications (13,16,40).…”

Section: Introductionmentioning

confidence: 99%

Human Adipose-Derived Stem Cells Accelerate the Restoration of Tensile Strength of Tendon and Alleviate the Progression of Rotator Cuff Injury in a Rat Model

Chen

Chan

et al. 2015

Cell Transplant

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Adult stem cell therapy for the treatment of tendon injuries is a growing area of research. This study is aimed to investigate the efficacy of human adipose-derived stem cell (hADSC) injection on the tendon during its healing process in a rat model of rotator cuff injury. hADSCs were injected 3 days after collagenase-induced rotator cuff injuries in experimental groups, while the control group received saline as a placebo. Histological and biomechanical analyses were performed 7, 14, 21, and 28 days after collagenase injection. Compared to the control group, it was found that inflammatory cells were significantly decreased in the hADSC-treated group after collagenase injection for 7 and 14 days. In the hADSC-injected group, the fiber arrangement and tendon organization had also been improved. On the seventh day after collagenase injection, the load to failure of the hADSC-injected group (15.87 ± 2.20 N) was notably higher than that of the saline-injected group (11.20 ± 1.35 N). It is suggested that the tensile strength of the supraspinatus tendon was significantly enhanced. Local administration of hADSCs might have the possibility to restore the tensile strength and attenuate the progression of tendinitis. Taken together, these findings demonstrate that the recovery processes in damaged tendons can be facilitated architecturally and functionally after hADSC injection.

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“…Inhibition of mTOR with the induction of autophagy can increase cell survival in neonatal models of ischemia (164) and during excitotoxicity (165). Autophagy protects cells during prion protein disease (166) and in models of Huntington’s disease (HD)(90, 167). Autophagy activation can reduce Aβ production and improve memory function in animal models of AD (168).…”

Section: Targeting Cell Death Through Mtormentioning

confidence: 99%

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

Maiese¹

2016

CNR

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Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. Yet, the biological and clinical outcome of these pathways can be complex especially with oversight of cell death mechanisms that involve apoptosis and autophagy. Growth factors, and in particular erythropoietin (EPO), are one avenue under consideration to implement control over cell death pathways since EPO can offer potential treatment for multiple disease entities and is intimately dependent upon mTOR signaling. In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies.

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ADSC Therapy in Neurodegenerative Disorders

Cited by 53 publications

References 87 publications

Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation

Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation

Human Adipose-Derived Stem Cells Accelerate the Restoration of Tensile Strength of Tendon and Alleviate the Progression of Rotator Cuff Injury in a Rat Model

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

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