CYBERMED LIFE - ORGANIC  & NATURAL LIVING

Cybermedlife - Therapeutic Actions Stem Cell Related Therapy

Stem cell factor-activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration. 📎

Abstract Title: Stem cell factor-activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration. Abstract Source: J Neurosci Res. 2014 Jul ;92(7):856-69. PMID: 24936617 Abstract Author(s): Tomoya Terashima, Hideto Kojima, Hiroshi Urabe, Isamu Yamakawa, Nobuhiro Ogawa, Hiromichi Kawai, Lawrence Chan, Hiroshi Maegawa Article Affiliation: Tomoya Terashima Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with motor neuron death. Several experimental treatments, including cell therapy using hematopoietic or neuronal stem cells, have been tested in ALS animal models, but therapeutic benefits have been modest. Here we used a new therapeutic strategy, bone marrow transplantation (BMT) with stem cell factor (SCF)- or FMS-like tyrosine kinase 3 (flt3)-activated bone marrow (BM) cells for the treatment of hSOD1(G93A) transgenic mice. Motor function and survival showed greater improvement in the SCF group than in the group receiving BM cells that had not been activated (BMT alone group), although no improvement was shown in the flt3 group. In addition, larger numbers of BM-derived cells that expressed the microglia marker Iba1 migrated to the spinal cords of recipient mice compared with the BMT alone group. Moreover, after SCF activation, but not flt3 activation or no activation, the migrating microglia expressed glutamate transporter-1 (GLT-1). In spinal cords in the SCF group, inflammatory cytokines tumor necrosis factor-α and interleukin-1β were suppressed and the neuroprotective molecule insulin-like growth factor-1 increased relative to nontreatment hSOD1(G93A) transgenic mice. Therefore, SCF activation changed the character of the migrating donor BM cells, which resulted in neuroprotective effects. These studies have identified SCF-activated BM cells as a potential new therapeutic agent for the treatment of ALS. Article Published Date : Jun 30, 2014

Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model.

Abstract Title: Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model. Abstract Source: Neuroscience. 2013 May 28 ;248C:333-343. Epub 2013 May 28. PMID: 23727509 Abstract Author(s): S Marconi, M Bonaconsa, I Scambi, G M Squintani, W Rui, E Turano, D Ungaro, S D'Agostino, F Barbieri, S Angiari, A Farinazzo, G Constantin, U Del Carro, B Bonetti, R Mariotti Article Affiliation: S Marconi Abstract: Therapeutic strategies for the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are actually minimally effective on patients' survival and quality of life. Although stem cell therapy has raised great expectations, information on the involved molecular mechanisms is still limited. Here we assessed the efficacy of the systemic administration of adipose-derived mesenchymal stem cells (ASC), a previously untested stem cell population, in superoxide-dismutase 1 (SOD1)-mutant transgenic mice, the animal model of familial ALS. The administration of ASC to SOD1-mutant mice at the clinical onset significantly delayed motor deterioration for 4-6weeks, as shown by clinical and neurophysiological tests. Neuropathological examination of ASC-treated SOD1-mutant mice at day 100 (i.e. the time of their best motor performance) revealed a higher number of lumbar motorneurons than in phosphate-buffered saline-treated SOD1-mutant mice and a restricted number of undifferentiated green fluorescent protein-labeled ASC in the spinal cord. By examining the spinal cord tissue factors that may prolong neuronal survival, we found a significant up-regulation in levels of glial-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) after ASC treatment. Considering that ASC produce bFGF but not GDNF, these findings indicate that ASC may promote neuroprotection either directly and/or by modulating the secretome of local glial cells toward a neuroprotective phenotype. Such neuroprotection resulted in a strong and long-lasting effect on motor performance and encourages the use of ASC in human pathologies, in which current therapies are not able to maintain a satisfying neurological functional status. Article Published Date : May 27, 2013

Linking respiratory chain uncoupling to amyotrophic lateral sclerosis implies potential treatment with herbal extracts containing genipin.

Abstract Title: Linking respiratory chain uncoupling to amyotrophic lateral sclerosis implies potential treatment with herbal extracts containing genipin. Abstract Source: Med Hypotheses. 2013 Mar ;80(3):327. Epub 2012 Dec 21. PMID: 23265356 Abstract Author(s): M Hoffmann Article Affiliation: M Hoffmann Abstract: No abstract. Article Published Date : Feb 28, 2013

Neural progenitors derived from human induced pluripotent stem cells survive and differentiate upon transplantation into a rat model of amyotrophic lateral sclerosis. 📎

Abstract Title: Neural progenitors derived from human induced pluripotent stem cells survive and differentiate upon transplantation into a rat model of amyotrophic lateral sclerosis. Abstract Source: Stem Cells Transl Med. 2013 Mar ;2(3):167-74. Epub 2013 Feb 14. PMID: 23413376 Abstract Author(s): Iuliana Ristea Popescu, Charles Nicaise, Song Liu, Grégoire Bisch, Sarah Knippenberg, Valery Daubie, Delphine Bohl, Roland Pochet Article Affiliation: Iuliana Ristea Popescu Abstract: Human induced pluripotent stem cells (iPSCs) offer hope for personalized regenerative cell therapy in amyotrophic lateral sclerosis (ALS). We analyzed the fate of human iPSC-derived neural progenitors transplanted into the spinal cord of wild-type and transgenic rats carrying a human mutated SOD1(G93A) gene. The aim was to follow survival and differentiation of human neural progenitors until day 60 post-transplantation in two different in vivo environments, one being ALS-like. iPSC-derived neural progenitors efficiently engrafted in the adult spinal cord and survived at high numbers. Different neural progenitor, astroglial, and neuronal markers indicated that, over time, the transplanted nestin-positive cells differentiated into cells displaying a neuronal phenotype in both wild-type and transgenic SOD1 rats. Although a transient microglial phenotype was detected at day 15, astroglial staining was negative in engrafted cells from day 1 to day 60. At day 30, differentiation toward a neuronal phenotype was identified, which was further established at day 60 by the expression of the neuronal marker MAP2. A specification process into motoneuron-like structures was evidenced in the ventral horns in both wild-type and SOD1 rats. Our results demonstrate proof-of-principle of survival and differentiation of human iPSC-derived neural progenitors in in vivo ALS environment, offering perspectives for the use of iPSC-based therapy in ALS. Article Published Date : Feb 28, 2013

Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of amyotrophic lateral sclerosis. 📎

Abstract Title: Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of amyotrophic lateral sclerosis. Abstract Source: Am J Respir Crit Care Med. 2013 Mar 1 ;187(5):535-42. Epub 2012 Dec 6. PMID: 23220913 Abstract Author(s): Nicole L Nichols, Genevieve Gowing, Irawan Satriotomo, Lisa J Nashold, Erica A Dale, Masatoshi Suzuki, Pablo Avalos, Patrick L Mulcrone, Jacalyn McHugh, Clive N Svendsen, Gordon S Mitchell Article Affiliation: Nicole L Nichols Abstract: RATIONALE: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1(G93A) rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. OBJECTIVES: To preserve or restore phrenic nerve activity in SOD1(G93A) rats at disease end stage. METHODS: SOD1(G93A) rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. MEASUREMENTS AND MAIN RESULTS: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. CONCLUSIONS: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. Article Published Date : Feb 28, 2013

Cultivating stem cells for treating amyotrophic lateral sclerosis. 📎

Abstract Title: Cultivating stem cells for treating amyotrophic lateral sclerosis. Abstract Source: World J Stem Cells. 2012 Dec 26 ;4(12):117-9. PMID: 23516096 Abstract Author(s): Shengwen Calvin Li, Hong Zhen Yin, William G Loudon, John H Weiss Article Affiliation: Shengwen Calvin Li Abstract: This editorial addresses the current challenges and future directions in the use of stem cells as an approach for treating amyotrophic lateral sclerosis. A wide variety of literature has been reviewed to enlighten the reader on the many facets of stem cell research that are important to consider before using them for a cell based therapy. Article Published Date : Dec 25, 2012

Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study. 📎

Abstract Title: Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study. Abstract Source: Neurol India. 2012 Sep-Oct;60(5):465-9. PMID: 23135021 Abstract Author(s): Sudesh Prabhakar, Neelam Marwaha, Vivek Lal, Ratti R Sharma, Roopa Rajan, Niranjan Khandelwal Article Affiliation: Sudesh Prabhakar Abstract: BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no effective treatment. Stem cell therapy may be one of the promising treatment options for such patients. AIM: To assess the feasibility, efficacy and safety of autologous bone marrow-derived stem cells in patients of ALS. SETTINGS AND DESIGN: We conducted an open-label pilot study of autologous bone marrow-derived stem cells in patients with ALS attending the Neurology Clinic of a tertiary care referral centre. MATERIALS AND METHODS: Ten patients with ALS with mean revised ALS Functional Rating Scale (ALSFRS-R) score of 30.2 (± 10.58) at baseline received intrathecal autologous bone marrow-derived stem cells. Primary end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point deterioration, median survival and reported adverse events. Paired t-test was used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was used for survival calculations. RESULTS: There was no significant deterioration in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090). The median survival post procedure was 18.0 months and median time to 4-point deterioration was 16.7 months. No significant adverse events were reported. CONCLUSION: Autologous bone marrow-derived stem cell therapy is safe and feasible in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend towards stabilization of disease. However, the benefit needs to be confirmed in the long-term follow-up period. Article Published Date : Aug 31, 2012

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