Adipose derived stem cells and nerve regeneration

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.

Neurogenic Differentiation of Murine Adipose Derived Stem Cells Transfected with EGFP in vitro

Some studies indicate that adipose derived stem cells(ADSCs)can differentiate into adipogenic,chondrogenic,myogenic,and osteogenic cells in vitro.However,whether ADSCs can be induced to differentiate into neural cells in vitro has not been clearly demonstrated.In this study,the ADSCs isolated from the murine adipose tissue were cultured and transfected with the EGFP gene,and then the cells were induced for neural differentiation.The morphology of those ADSCs began to change within two days which developed i...

Conditioned Medium from Human Umbilical Vein Endothelial Cells Promotes Proliferation,Migration,Invasion and Angiogenesis of Adipose Derived Stem Cells

Preeclampsia（PE） is a pregnancy-specific hypertensive complication,closely related to endothelial dysfunction.Adipose derived stem cells（ADSCs） have the capacity to differentiate into endothelial cells for vascular repair.Therefore,we hypothesized that induced endothelial differentiation of ADSCs might hold great potential for the treatment of PE.In this study,the primary ADSCs and human umbilical vein endothelial cells（HUVECs） were isolated by the collagenase digestion method.The supernatant of HUVECs was collected from the first generation of cells.Then,ADSCs were divided into two groups：ADSCs alone group and induced ADSCs（i ADSCs） group.In i ADSCs group,ADSCs were induced by HUVECs conditioned medium and ADSCs special culture medium at a ratio of 1：1 over a two-week period.In order to identify the endothelial characteristics of i ADSCs,CD31 and CD34 were examined by flow cytometry.The proliferation,migration,invasion and angiogenesis assays were employed to compare the bioactivity of i ADSCs and ADSCs.Furthermore,The levels of angiogenic related factors including vascular endothelial growth factor（VEGF） and placenta growth factor（Pl GF） were detected by RT-PCR and Western blotting.Results showed conditioned medium from HUVECs promoted ADSCs proliferation,migration,invasion and angiogenesis.In addition,the levels of VEGF and Pl GF were significantly enhanced in i ADSCs group.This study uncovered the i ADSCs application potential in the therapy and intervention of PE.

Osteogenesis of Adipose-Derived Stem Cells

Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.

Human adipose-derived mesenchymal stem cells： a better cell source for nervous system regeneration

Background In order to suggest an ideal source of adult stem cells for the treatment of nervous system diseases,MSCs from human adipose tissue and bone marrow were isolated and studied to explore the differences with regard to cell morphology,surface markers,neuronal differentiation capacity,especially the synapse structure formation and the secretion of neurotrophic factors.Methods The neuronal differentiation capacity of human mesenchymal stem cells from adipose tissue （hADSCs） and bone marrow （hBMSCs） was determined based on nissl body and synapse structure formation,and neural factor secretion function.hADSCs and hBMSCs were isolated and differentiated into neuron-like cells with rat brain-conditioned medium,a potentially rich source of neuronal differentiation promoting signals.Specific neuronal proteins and neural factors were detected by immunohistochemistry and enzyme-linked immunosorbent assay analysis,respectively.Results Flow cytometric analysis showed that both cell types had similar phenotypes.Cell growth curves showed that hADSCs proliferated more quickly than hBMSCs.Both kinds of cells were capable of osteogenic and adipogenic differentiation.The morphology of hADSCs and hBMSCs changed during neuronal differentiation and displayed neuronlike cell appearance after 14 days＇ differentiation.Both hADSCs and hBMSCs were able to differentiate into neuron-like cells based on their production of neuron specific proteins including β-tubulin-Ⅲ,neuron-specific enolase （NSE）,nissl bodies,and their ability to secrete brain derived neurotrophic factor （BDNF） and nerve growth factor （NGF）.Assessment of synaptop hysin and growth-associated protein-43 （GAP-43） suggested synapse structure formation in differentiated hADSCs and hBMSCs.Conclusions Our results demonstrate that hADSCs have neuronal differentiation potential similar to hBMSC,but with a higher proliferation capacity than hBMSC.Adipose tissue is abundant,easily available and would be a potential ideal source of adult stem cells for neural-related clinical research and application.

Adipose tissue derived stromal cells in a gelatin-based 3D matrix with exclusive ascorbic acid signalling emerged as a novel neural tissue engineering construct:an innovative prototype for soft tissue

The current study investigated a triad,which comprises of adipose tissue derived stem cells isolated from infrapatellar fat pad and gelatin/polyvinyl alcohol(PVA)-based matrix with exclusive ascorbic acid signalling.Though,the bio-mechanical properties of the gelatin–PVA blended scaffolds in wet condition are equivalent to the ECM of soft tissues in general,in this study,the triad was tested as a model for neural tissue engineering.Apart from being cytocompatible and biocompatible,the porosity of the scaffold has been designed in such a manner that it facilitates the cell signalling and enables the exchange of nutrients and gases.The highly proliferative stem cells from Passage 2 were characterized using both,mesenchymal and embryonic stem cell markers.As an initial exploration the mesenchymal stem cells at Passage 4 were exposed to ascorbic acid and basic fibroblast growth factor signalling for neuronal differentiation in 2D environment independently.The MSCs successfully differentiated and acquired neuron specific markers related to cytoskeleton and synapses.Subsequently,three phases of experiments have been conducted on the 3D gelatin/PVA matrix to prove their efficacy,the growth of stem cells,growth of differentiated neurons and the in situ growth and differentiation of MSCs.The scaffold was conducive and directed MSCs to neuronal lineage under specific signalling.Overall,this organotypic model triad could open a new avenue in the field of soft tissue engineering as a simple and effective tissue construct.

Nerve regeneration in vascularized composite allotransplantation:current strategies and future directions

Vascularized composite allotransplantation(VCA)has emerged as a viable treatment option for limb and face reconstruction of severe tissue defects.Functional recovery after VCA requires not only effective immunosuppression,but also consideration of peripheral nerve regeneration to facilitate motor and sensory reinnervation of donor tissue.At the time of transplantation,the donor and recipient nerves are typically coapted in an end-to-end fashion.Following transplantation,there are no therapies available to enhance nerve regeneration and graft reinnervation,and functional outcomes are dependent on the recipients’innate regenerative capacities.Functional outcomes to date have been promising,but there is still much room for improvement,studies have demonstrated reliable return of protective sensation(pain,thermal,gross tactile),while discriminative sensation and motor function show more inconsistent results.In order to maximize the benefit afforded to the by VCA,we must develop consistent and reliable procedures and therapies to ensure effective nerve regeneration and functional outcomes.New technologies,such as nerve guidance conduits and fibrin glues,and the use of stem cells to facilitate nerve regeneration remain untested in VCA but are proving worthwhile in the context of peripheral nerve repair.VCA presents a unique set of challenges with regards to surgical techniques,postoperative regimen,and health of donor tissue.In this review,we discuss current challenges underlying achievement of nerve regeneration in VCA and discuss novel technologies and approaches to translate nerve regeneration into functional restoration.