Health,Stem Cells, and Technology

Friday, August 24, 2012

A Small Molecule Modulator of Prion Protein Increases Human Mesenchymal Stem Cell Lifespan

Prion proteins are cell surface glycoproteins that, when in a misfolded configuration, are associated with, and may cause, diseases such as Creutzfeldt-Jakob disease, and "mad cow disease." Now, prion proteins have been shown to be important in stem cell physiology, and may be involved in the proliferation, differentiation, and release of SRM by adult stem cells.

Human mesenchymal stem cells (hMSCs) have been shown to have potential in regenerative approaches in bone and blood. Most protocols rely on their in vitro expansion prior to clinical use. However, several groups have shown that hMSCs lose proliferation and differentiation ability with serial passage in culture, limiting their clinical applications. Cellular prion protein (PrP) has been shown to enhance proliferation and promote self-renewal of hematopoietic, mammary gland, and neural stem cells. In this study from the UK, for the first time, that expression of PrP decreased in hMSC following ex vivo expansion. When PrP expression was knocked down, hMSC showed significant reduction in proliferation and differentiation. In contrast, hMSC expanded in the presence of small molecule 3/689, a modulator of PrP expression, showed retention of PrP expression with ex vivo expansion and extended lifespan up to 10 population doublings. Moreover, cultures produced a 300-fold increase in the number of cells generated. These cells showed a 10-fold increase in engraftment levels in bone marrow 5 weeks post-transplant. hMSC treated with 3/689 showed enhanced protection from DNA damage and enhanced cell cycle progression, in line with data obtained by gene expression profiling. Moreover, upregulation of superoxide dismutase-2 (SOD2) was also observed in hMSC expanded in the presence of 3/689. The increase in SOD2 was dependent on PrP expression and suggests increased scavenging of reactive oxygen species as mechanism of action.

These data suggest PrP as as part of a mechanism important to controlling stem cell physiology, enabling expansion and function, when used as an intervention in stem cell regenerative medicine and therapeutics. Stem Cells2012;30:1134–1143

Friday, August 3, 2012

Dietary Therapy Promotes Neuroprotection In Chronic Spinal Cord Injury

The pathogenesis of cervical spondylotic myelopathy (CSM), spinal cord injury, is related to both primary mechanical and secondary biological injury. Surgical management of CSM has undergone significant improvement in the past few decades, better addressing the primary mechanical injury. Despite advancements in spinal instrumentation and operative technique, however, neurological recovery can still be relatively limited in most patients following surgery. our greatest challenge in treating patients with CSM is an inability to directly treat the insidious secondary biological injury that ubiquitously occurs with this disorder.

In recent years there has been increasing interest in the influence of dietary factors on specific molecular systems and mechanisms within the CNS. In particular, the omega-3 fatty acid DHA (fish oil for example) has shown therapeutic potential based on its effects in reducing inflammation and providing structural material to plasma membranes, and on its effects on overall neuronal function. Also, curcumin (contained in turmeric)  possesses strong antiinflammatory and antioxidant capacity such that the combined actions of DHA and curcumin could be a potential strategy to counteract the biological injury encountered in CSM.

In a rat model, researchers at UCLA School of Medicine, revealed significantly worse function in the traditional diet group than in the DHA-Curcumin group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Curcumin group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Curcumin animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane. This study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy.

Holly LT et al, Journal of Neurosurgery: Spine

Aug 2012 / Vol. 17 / No. 2 / Pages 134-140