Growth factor in stem cells may spur recovery from MS

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Growth factor in stem cells may spur recovery from MS

Postby MSUK » Mon May 21, 2012 6:54 am

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A substance in human mesenchymal stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found.

Their study appeared in the online version of Nature Neuroscience on Sunday, May 20.

In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease.

"The importance of this work is we think we've identified the driver of the recovery," said Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1405
MS-UK - http://www.ms-uk.org/
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Re: Growth factor in stem cells may spur recovery from MS

Postby questor » Mon May 21, 2012 8:05 am

The relationship between exercise and human growth factors is very relevant:

http://content.onlinejacc.org/cgi/conte ... 43/12/2314

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Re: Growth factor in stem cells may spur recovery from MS

Postby Liberation » Fri May 25, 2012 10:47 am

Could Stem Cells Cure MS?
A growth factor isolated from human stem cells shows promising results in a mouse model of multiple sclerosis.

By Megan Scudellari | May 23, 2012

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A human mesenchymal stem cell
Wikimedia Commons, GhansonHuman mesenchymal stem cells (hMSCs) have become a popular potential therapy for numerous autoimmune and neurological disorders. But while these bone marrow-derived stem cells have been studied in great detail in the dish, scientists know little about how they modulate the immune system and promote tissue repair in living organisms.

Now, one research team has uncovered a molecular mechanism by which hMSCs promote recovery in a mouse model of multiple sclerosis (MS).

According to research, published online Sunday (May 20) in Nature Neuroscience, a growth factor produced by hMSCs fights MS in two ways: blocking a destructive autoimmune response and repairing neuronal damage. The finding could help advance ongoing clinical trials testing hMSCs as a therapy for MS.

The researchers have identified “a unique factor that has surprisingly potent activity mediating neuron repair,” said Jacques Galipeau, a cell therapy researcher at Emory University in Atlanta, Georgia, who was not involved in the research. “The magnitude of the effect on a mouse model of MS is a big deal.”

MS is an autoimmune disease in which the immune system attacks myelin sheaths that surround and protect nerve cells. The attack leaves nerves exposed and unable to send signals to the brain and back, resulting in the loss of motor skills, coordination, vision, and cognitive abilities. There is no cure for MS, and most current therapies work to simply suppress the immune system, preventing further neuronal damage. None have demonstrated an ability to also repair damaged myelin and promote recovery.

In 2009, Robert Miller and colleagues at Case Western Reserve University in Cleveland, Ohio, demonstrated that hMSCs dramatically reversed the symptoms of multiple sclerosis in a mouse model of the disorder. “The animals got better,” recalled Miller. The team hypothesized that the stem cells suppress the immune response and promote remyelination.

But Miller wanted to know exactly what the cells were doing. To find out, his team isolated the medium on which the hMSCs were grown to determine if the cells or something they secreted was responsible for the observed recovery. The medium alone was enough to induce recovery in mice, pointing to the latter.

To find out exactly which molecule or molecules in the medium were responsible, the researchers separated the proteins in the fluid based on the molecular weight and injected each isolate into mice exhibiting symptoms of MS. The mid-weight solution, of proteins with masses between 50 and 100 kilodaltons (kDa), caused recovery. “That eliminated a huge number of potential candidates,” said Miller.

The researchers then narrowed the field again with a literature search for a molecule that fit their criteria: secreted by hMSCs, 50-100 kDa in size, and involved in tissue repair. They identified hepatocyte growth factor (HGF), a cytokine made by mesenchymal cells that has been shown to promote tissue regeneration and cell survival in numerous experiments. Sure enough, HGF alone was enough to promote recovery in the MS mouse models, and blocking the receptor for HGF in those mice blocked recovery. The team also demonstrated that HGF suppresses immune responses in vivo and accelerates remyelination of neurons in vitro. Finally, they saw that HGF causes remyelination in rats with a lesion on their spinal cord.

“I feel quite confident that HGF suppresses the immune response and also drives myelin repair,” said Miller. There are likely other hMSCs-produced factors that contribute to the cells’ beneficial effect, but HGF is certainly critical, he said. “The data are compelling,” added Galipeau.

There are currently several clinical trials testing hMSCs in MS patients around the world, including a phase I trial at the Cleveland Clinic in Ohio that emerged from the work in Miller’s lab. The new mechanistic information could help researchers designing those therapies to select cells that produce high levels of HGF, said Miller, which should promote remyelination and maximize symptom reversal.

But the research begs a question: why not simply forgo the cells altogether? That point is up for debate. Miller argues that stem cells act as vehicles to transport HGF, and other potential factors, directly to the central nervous system and maintain production there. But a single protein is a far more practical therapy—cheaper and easier to produce—than a cell therapy, countered Galipeau. “The best cell therapy is one done without a cell,” he said. “Identifying these factors and testing them as single agents is an important short-term deliverable of stem cell science.”

To find out more about which cell therapies are in clinical trials, stay tuned for the July issue of The Scientist, featuring an analysis of the growing cell therapy industry.

L. Bai et al., “Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models,” Nat Neuro, doi:10.1038/nn.3109, 2012.
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Re: Growth factor in stem cells may spur recovery from MS

Postby lyndacarol » Fri May 25, 2012 3:03 pm

And then there is this:

Growth factor was mentioned in the Winter 08-09 issue of the MS Society publication named Momentum:

"The growth factor IGF-1 had shown some success in promoting myelin formation, so a Society-funded team led by Stephane Genoud, PhD (The Salk Institute, La Jolla, Calif.), injected it into mice with EAE. The injections actually worsened the disease. (Journal of Neuroimmunology 2005; 168:40-5) Such failures are important to pinpoint before they affect people with MS in clinical trials."

Here is the abstract of the work mentioned:

1: J Neuroimmunol. 2005 Nov;168(1-2):40-5. Epub 2005 Aug 24. Links
Targeted expression of IGF-1 in the central nervous system fails to protect mice from experimental autoimmune encephalomyelitis.Genoud S, Maricic I, Kumar V, Gage FH.
Laboratory of Genetics, The Salk Institute, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.

Insulin-like growth factor 1 (IGF-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (CNS). Systemic injection of IGF-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (EAE). Since systemic IGF-1 can also modulate peripheral immune lymphocytes, we examined whether a sustained and local delivery of IGF-1 into the spinal cord would have any influence on the chronic course of EAE in C57/BL6 mice. The capability of adeno-associated virus (AAV) to be retrogradely transported efficiently from muscle to motor neurons of the spinal cord was used to overcome the difficulty routinely encountered when attempting chronic delivery of molecules into the CNS. We demonstrate that AAV-mediated delivery of IGF-1 in CNS did not have any beneficial effect on the clinical course of EAE. Injection of AAV-IGF1 after induction of the disease worsened the clinical symptoms. Furthermore, CNS expression of IGF-1 did not affect the pathogenic anti-MOG T cell response, as examined by proliferation and cytokine secretion. Thus, enhanced expression of IGF-1 in the CNS during inflammation does not have a significant effect on myelination. These data have important implications for the potential use of IGF-1 in the treatment of multiple sclerosis.

PMID: 16120466 [PubMed - indexed for MEDLINE]
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Re: Growth factor in stem cells may spur recovery from MS

Postby Liberation » Sat May 26, 2012 10:09 am

lyndacarol wrote:And then there is this:

Growth factor was mentioned in the Winter 08-09 issue of the MS Society publication named Momentum:

"The growth factor IGF-1 had shown some success in promoting myelin formation, so a Society-funded team led by Stephane Genoud, PhD (The Salk Institute, La Jolla, Calif.), injected it into mice with EAE. The injections actually worsened the disease. (Journal of Neuroimmunology 2005; 168:40-5) Such failures are important to pinpoint before they affect people with MS in clinical trials."

Here is the abstract of the work mentioned:

1: J Neuroimmunol. 2005 Nov;168(1-2):40-5. Epub 2005 Aug 24. Links
Targeted expression of IGF-1 in the central nervous system fails to protect mice from experimental autoimmune encephalomyelitis.Genoud S, Maricic I, Kumar V, Gage FH.
Laboratory of Genetics, The Salk Institute, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.

Insulin-like growth factor 1 (IGF-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (CNS). Systemic injection of IGF-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (EAE). Since systemic IGF-1 can also modulate peripheral immune lymphocytes, we examined whether a sustained and local delivery of IGF-1 into the spinal cord would have any influence on the chronic course of EAE in C57/BL6 mice. The capability of adeno-associated virus (AAV) to be retrogradely transported efficiently from muscle to motor neurons of the spinal cord was used to overcome the difficulty routinely encountered when attempting chronic delivery of molecules into the CNS. We demonstrate that AAV-mediated delivery of IGF-1 in CNS did not have any beneficial effect on the clinical course of EAE. Injection of AAV-IGF1 after induction of the disease worsened the clinical symptoms. Furthermore, CNS expression of IGF-1 did not affect the pathogenic anti-MOG T cell response, as examined by proliferation and cytokine secretion. Thus, enhanced expression of IGF-1 in the CNS during inflammation does not have a significant effect on myelination. These data have important implications for the potential use of IGF-1 in the treatment of multiple sclerosis.

PMID: 16120466 [PubMed - indexed for MEDLINE]


Hi Linda,

I am definitely not an expert in this field, but IGF is not HGF. That is for sure. HGF is a hepatocyte growth factor. There are also human experiments preceeding the use of HGF alone. There were quite a few people who went through MSC infusions with some success in the past in different hospitals. This is why there are several clinical trials in 1st and 2nd phase where they test the effectiveness of MSC. No adverse effects so far.

The positive impacts of the MSC treatments drew the attention of the researchers to find out what elements of the MSC have positive effects. This is how they arrived at HGF. They tested it on mice with positive results. This is where they stand now.
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