In part 2, Dr. Riordan discusses case studies of spinal cord injury patients treated with CD34+ and mesenchymal stem cells harvested from human umbilical cord wharton's jelly and cord blood, animal studies using mesenchymal stem cells, immunosuppression requirements in allogeneic stem cell treatments, intrathecal and intravenous administration of autologous bone marrow stem cells in spinal cord injury patients, and the role adult stem cell trophic factors in tissue regeneration.
Tuesday, May 22, 2012
Monday, May 21, 2012
Multiple Sclerosis Treatment Success Using Mesenchymal Stem Cell-Secreted Factors in Animal Model
Stem cell researchers at Case Western Reserve have reported in Nature Magazine that the functional deficits caused by multiple sclerosis can be reduced by administering mesenchymal stem cell secreted factors.
While previous studies have shown promising results using mesenchymal stem cells, this is the first time that such results have been reported without using the stem cells themselves.
The Stem Cell Institute's Founder, Neil Riordan PhD, originally cited the potential therapeutic role of mesenchymal stem cell trophic factors in the 2010 Cellular Immunology publication: Mesenchymal Stem Cells as Anti-inflammatories: Implications for Treatment of Duchenne Muscular Dystrophy
In addition to reducing functional deficits, the development of new myelinating oligodendrocytes and neurons, release of inflammatory cytokines, and suppression of immune cells influx were also observed in the Case Western study.
Details can be found here:
http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.3109.html
Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models
Lianhua Bai, Donald P Lennon, Arnold I Caplan, Anne DeChant, Jordan Hecker, Janet Kranso, Anita Zaremba Robert H Miller
Nature Neuroscience (2012) doi:10.1038/nn.3109
Received 18 January 2012 Accepted 17 April 2012 Published online 20 May 2012
Abstract
Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.
While previous studies have shown promising results using mesenchymal stem cells, this is the first time that such results have been reported without using the stem cells themselves.
The Stem Cell Institute's Founder, Neil Riordan PhD, originally cited the potential therapeutic role of mesenchymal stem cell trophic factors in the 2010 Cellular Immunology publication: Mesenchymal Stem Cells as Anti-inflammatories: Implications for Treatment of Duchenne Muscular Dystrophy
In addition to reducing functional deficits, the development of new myelinating oligodendrocytes and neurons, release of inflammatory cytokines, and suppression of immune cells influx were also observed in the Case Western study.
Details can be found here:
http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.3109.html
Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models
Lianhua Bai, Donald P Lennon, Arnold I Caplan, Anne DeChant, Jordan Hecker, Janet Kranso, Anita Zaremba Robert H Miller
Nature Neuroscience (2012) doi:10.1038/nn.3109
Received 18 January 2012 Accepted 17 April 2012 Published online 20 May 2012
Abstract
Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.
Friday, May 18, 2012
Neil Riordan PhD - Stem Cell Therapy for Spinal Cord Injury (Video part 1 of 5)
Part 1: The Stem Cell Institute's Founder, Dr. Neil Riordan discusses mesenchymal stem cells from umbilical cord Wharton's jelly, stem cell expansion, therapeutic potential of umbilical cord mesenchymal stem cells vs. bone marrow mesenchymal stem cells, CD34+ hematopoietic stem cells from umbilical cord blood and the scientific rationale supporting stem cell treatment of spinal cord injury
Friday, May 11, 2012
Latest Stem Cell Therapy Protocol for Multiple Sclerosis
For the latest information on combination stem cell treatment protocol for MS using the patient's own adipose-derived mesenchymal stem cells and donated human umbilical cord tissue-derived mesenchymal stem cells, please visit:
http://www.cellmedicine.com/treatment/multiple-sclerosis/
http://www.cellmedicine.com/treatment/multiple-sclerosis/
Wednesday, May 9, 2012
Adult Stem Cells Successfully Treat Spinal Cord Injury
An interesting spinal cord injury study was published last week. The Turkish researchers tested two types of stem cells on spinal cord injured mice. The two cell types were native bone marrow cells and cultured repair stem cells called Mesenchymal stem cells. Native bone marrow cells contain bone marrow forming stem cells as well as a small number of Mesenchymal stem cells.
After injuring the spinal cords, the stem cells were implanted at the site of the injury. The control mice that received no cells had no improvement in neural activity. The mice that received both cell types had improved neural activity. The cultured Mesenchymal stem cell group improved significantly more than the native bone marrow stem cell group.
Stem Cell Rev. 2012 May 3. [Epub ahead of print]
Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells.
Ozdemir M, Attar A, Kuzu I, Ayten M, Ozgencil E, Bozkurt M, Dalva K, Uckan D, Kılıc E, Sancak T, Kanpolat Y, Beksac M.
Source
School of Medicine, Department of Neurosurgery, Pamukkale University, 20070, Kinikli, Denizli, Turkey, drmevci@hotmail.com.
Abstract
OBJECTIVE:
The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally.
MATERIALS AND METHODS:
The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells.
RESULTS:
All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP(+)Luc(+) neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48-64 % and 68-72 %; 44-80 %; 8 and 18 within Groups III and IV respectively.
DISCUSSION:
MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.
After injuring the spinal cords, the stem cells were implanted at the site of the injury. The control mice that received no cells had no improvement in neural activity. The mice that received both cell types had improved neural activity. The cultured Mesenchymal stem cell group improved significantly more than the native bone marrow stem cell group.
Stem Cell Rev. 2012 May 3. [Epub ahead of print]
Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells.
Ozdemir M, Attar A, Kuzu I, Ayten M, Ozgencil E, Bozkurt M, Dalva K, Uckan D, Kılıc E, Sancak T, Kanpolat Y, Beksac M.
Source
School of Medicine, Department of Neurosurgery, Pamukkale University, 20070, Kinikli, Denizli, Turkey, drmevci@hotmail.com.
Abstract
OBJECTIVE:
The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally.
MATERIALS AND METHODS:
The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells.
RESULTS:
All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP(+)Luc(+) neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48-64 % and 68-72 %; 44-80 %; 8 and 18 within Groups III and IV respectively.
DISCUSSION:
MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.
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