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1.
Brain Res ; 1530: 82-105, 2013 Sep 12.
Article in English | MEDLINE | ID: mdl-23872219

ABSTRACT

The sex hormone progesterone has been shown to improve outcomes in animal models of a number of neurologic diseases, including traumatic brain injury, ischemia, spinal cord injury, peripheral nerve injury, demyelinating disease, neuromuscular disorders, and seizures. Evidence suggests it exerts its neuroprotective effects through several pathways, including reducing edema, improving neuronal survival, and modulating inflammation and apoptosis. In this review, we summarize the functional outcomes and pathophysiologic mechanisms attributed to progesterone treatment in neurologic disease. We then comment on the breadth of evidence for the use of progesterone in each neurologic disease family. Finally, we provide support for further human studies using progesterone to treat several neurologic diseases.


Subject(s)
Brain Injuries/metabolism , Nervous System Diseases/metabolism , Neuroprotective Agents/metabolism , Progesterone/metabolism , Spinal Cord Injuries/metabolism , Animals , Brain Injuries/prevention & control , Humans , Nervous System Diseases/prevention & control , Spinal Cord Injuries/prevention & control
2.
Tissue Eng Part A ; 15(10): 3129-38, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19344289

ABSTRACT

Insufficient availability of osteogenic cells limits bone regeneration through cell-based therapies. This study investigated the potential of amniotic fluid-derived stem (AFS) cells to synthesize mineralized extracellular matrix within porous medical-grade poly-epsilon-caprolactone (mPCL) scaffolds. The AFS cells were initially differentiated in two-dimensional (2D) culture to determine appropriate osteogenic culture conditions and verify physiologic mineral production by the AFS cells. The AFS cells were then cultured on 3D mPCL scaffolds (6-mm diameter x 9-mm height) and analyzed for their ability to differentiate to osteoblastic cells in this environment. The amount and distribution of mineralized matrix production was quantified throughout the mPCL scaffold using nondestructive micro computed tomography (microCT) analysis and confirmed through biochemical assays. Sterile microCT scanning provided longitudinal analysis of long-term cultured mPCL constructs to determine the rate and distribution of mineral matrix within the scaffolds. The AFS cells deposited mineralized matrix throughout the mPCL scaffolds and remained viable after 15 weeks of 3D culture. The effect of pre-differentiation of the AFS cells on the subsequent bone formation in vivo was determined in a rat subcutaneous model. Cells that were pre-differentiated for 28 days in vitro produced seven times more mineralized matrix when implanted subcutaneously in vivo. This study demonstrated the potential of AFS cells to produce 3D mineralized bioengineered constructs in vitro and in vivo and suggests that AFS cells may be an effective cell source for functional repair of large bone defects.


Subject(s)
Amniotic Fluid/cytology , Minerals/metabolism , Stem Cells/cytology , Stem Cells/metabolism , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Biocompatible Materials/chemistry , Caproates/chemistry , Cell Survival , Cells, Cultured , Extracellular Matrix/metabolism , Humans , Lactones/chemistry , Polymers/chemistry , Spectroscopy, Fourier Transform Infrared
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