Cell transplantation
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Cell transplantation · Oct 2016
Autogenous Mesenchymal Stem Cells from the Vertebral Body Enhance Intervertebral Disc Regeneration via Paracrine Interaction: An in Vitro Pilot Study.
Several in vivo studies have found that transplanting mesenchymal stem cells (MSCs) into degenerative intervertebral discs (IVDs) leads to regeneration of disc cells. Since the exact underlying mechanisms are not understood, we investigated the mechanisms of action of MSCs in regeneration of degenerative IVDs via paracrine actions. Human MSCs and degenerative disc cells from the same donor vertebrae were directly or indirectly cocultured. ⋯ During coculturing, MSCs downregulated the expression levels of various proinflammatory cytokine genes in degenerative NP [interleukin-1α ( IL-1α), IL-1β, IL-6, and tumor necrosis factor-α ( TNF-α)] and AF cells ( IL-1α and IL-6), which are involved in the degradation of ECM molecules. In association with the trophic effect of MSCs on degenerative disc cells, upregulation of growth factor mRNA expression was shown in MSCs cocultured with degenerative NP cells [epidermal growth factor ( EGF), insulin-like growth factor-1 ( IGF-1), osteogenic protein-1 ( OP-1), growth and differentiation factor-7 ( GDF-7), and transforming growth factor-β ( TGF-β)] or degenerative AF cells ( IGF-1, OP-1, and GDF-7). In terms of MSC-based clinical approaches to IVD regeneration, implanting MSCs into a degenerative IVD may both stimulate MSC differentiation into an NP- or AF-like phenotype and stimulate the biological activation of degenerative disc cells for self-repair.
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Cell transplantation · Oct 2016
Human Neural Stem Cell Transplantation-Mediated Alteration of Microglial/Macrophage Phenotypes after Traumatic Brain Injury.
Neural stem cells (NSCs) promote recovery from brain trauma, but neuronal replacement is unlikely the sole underlying mechanism. We hypothesize that grafted NSCs enhance neural repair at least partially through modulating the host immune response after traumatic brain injury (TBI). C57BL/6 mice were intracerebrally injected with primed human NSCs (hNSCs) or vehicle 24 h after a severe controlled cortical impact injury. ⋯ These phenotypic switches were accompanied by the increased expression of anti-inflammatory interleukin-4 receptor α and decreased proinflammatory interferon-γ receptor β. Finally, grafted hNSCs mainly differentiated into neurons and were phagocytized by either M1 or M2 microglia/macrophages. Thus, intracerebral transplantation of primed hNSCs efficiently leads host microglia/macrophages toward an anti-inflammatory phenotype that presumably contributes to stem cell-mediated neuroprotective effects after severe TBI in mice.
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Cell transplantation · Jan 2016
Intrathecal Transplantation of Embryonic Stem Cell-Derived Spinal GABAergic Neural Precursor Cells Attenuates Neuropathic Pain in a Spinal Cord Injury Rat Model.
Neuropathic pain following spinal cord injury (SCI) is a devastating disease characterized by spontaneous pain such as hyperalgesia and allodynia. In this study, we investigated the therapeutic potential of ESC-derived spinal GABAergic neurons to treat neuropathic pain in a SCI rat model. Mouse embryonic stem cell-derived neural precursor cells (mESC-NPCs) were cultured in media supplemented with sonic hedgehog (SHH) and retinoic acid (RA) and efficiently differentiated into GABAergic neurons. ⋯ The engrafted spinal GABAergic neurons remarkably increased both the paw withdrawal threshold (PWT) below the level of the lesion and the vocalization threshold (VT) to the level of the lesion (T12, T11, and T10 vertebrae), which indicates attenuation of chronic neuropathic pain by the spinal GABAergic neurons. The transplanted cells were positive for GABA antibody staining in the injured region, and cells migrated to the injured spinal site and survived for more than 7 weeks in L4-L5. The mESC-NPC-derived spinal GABAergic neurons dramatically attenuated the chronic neuropathic pain following SCI, suggesting that the spinal GABAergic mESC-NPCs cultured with low doses of SHH and RA could be alternative cell sources for treatment of SCI neuropathic pain by stem cell-based therapies.
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Cell transplantation · Jan 2016
Randomized Controlled TrialAutologous Olfactory Lamina Propria Transplantation for Chronic Spinal Cord Injury: Three-Year Follow-Up Outcomes From a Prospective Double-Blinded Clinical Trial.
We did a clinical trial to determine whether olfactory mucosa lamina propria (OLP) transplants promote regeneration and functional recovery in chronic human spinal cord injury (SCI). The trial randomized 12 subjects to OLP transplants (n = 8) or control sham surgery (n = 4). The subjects received magnetic resonance imaging (MRI), electromyography (EMG), urodynamic study (UDS), American Spinal Injury Association impairment scale (AIS), and other functional assessments. ⋯ At 3 years after OLP transplant, one patient improved from AIS A to C and another recovered from AIS A to B, two recovered more than three segmental sensory levels, two had less spasticity, two had altered H-reflexes and SSEP, two regained bladder and anorectal sensation and had improved bladder compliance on UDS. OLP-treated patients had partial or complete tissue bridges at the injury site compared to cavitary gaps in sham-operated patients. The limited recovery suggests that OLP transplants alone do not have significant benefits but may provide a rationale for larger randomized trials or combination therapies.
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Cell transplantation · Jan 2016
Adipose-Derived Stem Cells Accelerate Diabetic Wound Healing Through the Induction of Autocrine and Paracrine Effects.
Cell-based therapy is an attractive approach for the treatment of chronic nonhealing wounds. This study investigated whether adipose-derived stem cells (ASCs) can accelerate diabetic wound healing and traffic in the engraftment of ASCs. Dorsal full-thickness skin wound defects (6 × 5 cm) were created in a streptozotocin (STZ)-induced diabetes rodent model. ⋯ IVIS analysis revealed ASCs could exist and home into the periwound area up to 8 weeks postimplantation. In conclusion, ASCs significantly enhanced diabetic wound healing, engrafted into the local wound tissue, and implanted into circulating blood. ASC treatment stimulated neoangiogenesis and increased tissue regeneration through paracrine and autocrine mechanisms.