Differentiation Of Endogenous Cells Research Articles

Bioactive Film-Guided Soft-Hard Interface Design Technology for Multi-Tissue Integrative Regeneration.

Control over soft‐to‐hard tissue interfaces is attracting intensive worldwide research efforts. Herein, a bioactive film‐guided soft–hard interface design (SHID) for multi‐tissue integrative regeneration is shown. Briefly, a soft bioactive film with good elasticity matchable to native ligament tissue, is incorporated with bone‐mimic components (calcium phosphate cement, CPC) to partially endow the soft‐film with hard‐tissue mimicking feature. The hybrid film is elegantly compounded with a clinical artificial ligament to act as a buffer zone to bridge the soft (ligament) and hard tissues (bone). Moreover, the bioactive film‐decorated ligament can be rolled into a 3D bio‐instructive implant with spatial‐controllable distribution of CPC bioactive motifs. CPC then promotes the recruitment and differentiation of endogenous cells in to the implant inside part, which enables a vascularized bone growth into the implant, and forms a structure mimicking the biological ligament–bone interface, thereby significantly improving osteointegration and biomechanical property. Thus, this special design provides an effective SHID‐guided implant‐bioactivation strategy unreached by the traditional manufacturing methods, enlightening a promising technology to develop an ideal SHID for translational use in the future.

Effect of active factor on proliferation and differentiation of endogenous neural stem cells after traumatic brain injury in rats

Objective To investigate the effect of active factor on proliferation and differentiation of neural stem cells(NSCs)in the hippocampal subgranular zone after traumatic brain injury(TBI)in rats. Methods SD rats were divided into sham-injured group (only left dura mater exposed), active factor group (sham injury+ active factor therapy), TBI group (unilateral fluid percussion was used to generate severe TBI), and TBI+ active factor group (TBI+ active factor therapy) according to the random number table (n=10 in each group). Hippocampal homogenates or brain tissues were harvested at 7 d postinjury. Expressions of BrdU and NeuN in the hippocampal subgranular zone were detected by immunofluorescence staining, and five consecutive sections were used to count BrdU and NeuN positive cells. Level of nuclear factor (NF)-κB p65 in hippocampus was detected by Western blot. Results Number of BrdU and NeuN positive cells in TBI group were greatly higher than that in sham-injured group (P 0.05). NF-κBp65 presented over-expression in TBI group (0.81±0.09) while reversed in TBI+ active factor group (1.46±0.13), when compared to sham-injured group (P 0.05). Conclusion Active factor therapy can promote proliferation and neuronal differentiation of NSCs in the hippocampal subgranular zone after TBI in rats and the possible mechanism may relate to activation of the NSCs and inhibition of over-expression of NF-κBp65. Key words: Craniocerebral trauma; Neural stem cells; Active factor

The effects of functional electrical stimulation on motor function and on the proliferation, migration and differentiation of neural stem cells in the subventricular zone

Objective To investigate the effects of functional electrical stimulation (FES) on motor function and on the expression, proliferation, migration and differentiation of endogenous neural stem cells in the subventricular zone (SVZ) after cerebral ischemia. Methods Middle cerebral artery occlusion (MCAO) was used to induce a model of cerebral ischemia in 108 rats using the modified Zea-Longa method of intraluminal filament occlusion. They were then randomly divided into an FES group, a placebo stimulation group and a control group with 36 cases in each. Superficial FES electrodes were pasted on the paralyzed forelimbs of the rats in the first two groups, though FES treatment was administered only to the FES group beginning on the 3rd day after the MCAO operation. The stimulation was designed to produce extension of the wrist and digits of the paralyzed forelimb. Before, and after 1, 3, 7 and 14 days of the treatment, the neurological deficit was evaluated using modified neurological severity scoring (mNSS). BrdU+ /GFAP+ , BrdU+ /DCX+ and BrdU+ /NeuN+ cells in the SVZ were detected using immunofluorescence technique. Results After 7 and 14 days of treatment, the average motor function of the rats in the FES group had improved significantly when compared with the averages of the other two groups. Compared with the other two groups, the average number of BrdU+ /GFAP+ positive cells in the ischemic SVZ was also significantly greater in the FES group after 7 and 14 days of treatment. After 14 days, BrdU+ /Dcx+ positive cells in the FES group had also increased significantly more, but only a few BrdU+ /NeuN+ cells had appeared in any of the three groups. Conclusion FES can improve motor function after cerebral ischemia, and promote proliferation and differentiation of neural stem cells in the SVZ. Key words: Electrical stimulation; Brain ischemia; Functional electrical stimulation; Neural stem cells; Subventricular zone

Differentiation of endogenous neural stem cells in adult versus neonatal rats after brachial plexus root avulsion injury.

An experimental model of brachial plexus root avulsion injury of cervical dorsal C5-6 was established in adult and neonatal rats. Real-time PCR showed that the levels of brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 in adult rats increased rapidly 1 day after brachial plexus root avulsion injury, and then gradually decreased to normal levels by 21 days. In neonatal rats, levels of the three neurotrophic factors were decreased on the first day after injury, and then gradually increased from the seventh day and remained at high levels for an extended period of time. We observed that greater neural plasticity contributed to better functional recovery in neonatal rats after brachial plexus root avulsion injury compared with adult rats. Moreover, immunohistochemical staining showed that the number of bromodeoxyuridine/nestin-positive cells increased significantly in the spinal cords of the adult rats compared with neonatal rats after brachial plexus root avulsion injury. In addition, the number of bromodeoxyuridine/glial fibrillary acidic protein-positive cells in adult rats was significantly higher than in neonatal rats 14 and 35 days after brachial plexus injury. Bromodeoxyuridine/β-tubulin-positive cells were not found in either adult or neonatal rats. These results indicate that neural stem cells differentiate mainly into astrocytes after brachial plexus root avulsion injury. Furthermore, the degree of neural stem cell differentiation in neonatal rats was lower than in adult rats.

Regeneration of the mammalian inner ear sensory epithelium

This review will focus on 'self-repair' of the mammalian inner ear sensory epithelium, including recruiting the in-situ proliferation and differentiation of endogenous cells at the damaged site and the autologous transplantation Self-repair refers to a favorable structural and functional outcome of damaged inner ear sensory epithelium. Our advanced ability of manipulating the fate of inner ear sensory cells makes in-situ proliferation a possible candidate of hearing restoration. A practical alternative of the unavoidable immune rejection is to introduce autologous cells. Ependymal cells, induced pluripotent stem cells, and olfactory neuroepithelial cells have been recognized as promising sources, which will spur ongoing efforts to evaluate these new cell sources for cell replacement therapy. Further exploration of the innate advantages of in-situ proliferation and use of novel cell sources for autologous transplantation may serve as rehearsals for clinical trials in the near future.

Influences of bFGF and EGF on the proliferation and differentiation of endogenous neural stem cells after cerebral infarction in human

To investigate the relationship of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) and proliferation of endogenous neural stem cells (NSCs) after human cerebral infarction. Paraffin-embedded brain tissues of 22 human fatal cases of CI from the brain tissues around subventricular zone and subgranular layer zone were stained with HE and immunohistochemistry stain. The endogenous neural stem cells were marked by nestin. The expression changes of EGF, bFGF and nestin in the perihematomal tissues were analysed with the SPSS 13.0 system. (1) Compared with the controls, the number of nestin-positive cells increased at 24 - 72 h (14 +/- 6)/HP in the ipsilateral SVZ and began to rise at 4.5 - 10 h (11 +/- 5)/HP in the ipsilateral SGZ, reached maximum at 120 - 144 h ((38 +/- 7)/HP in the SVZ, (54 +/- 17)/HP in the SGZ, and decreased markedly at 216 - 336 h, but it was still elevated compared with the controls (P < 0.05). (2) The number of bFGF-positive cells increased at 4.5 - 10 h (8.1 +/- 2.9)/HP in the SVZ, (19.0 +/- 8.2)/HP in the SGZ, reached maximum at 24 - 70 h (15.6 +/- 3.5)/HP in the SVZ, (32.0 +/- 5.7)/HP in the SGZ and decreased at 72 - 96 h, but it was still elevated compared with the controls (P < 0.05). (3) The number of EGF-positive cells increased at 4.5 - 10 h (4.3 +/- 1.6)/HP in the SVZ, (7.0 +/- 3.7)/HP in the SGZ, reached maximum at 120 - 144 h (27.0 +/- 1.4)/HP in the SVZ, (51.5 +/- 4.9)/HP in the SGZ and decreased at 216 - 336 h, but it was still elevated compared with the controls (P < 0.05). Perhaps the increased expression of EGF and bFGF after CI was a reaction of endogenous reparation and it correlated with the proliferation and endogenous of neural stem cells in human.

Stem cells for neurodegenerative disorders: where can we go from here?

The use of stem cells in cell replacement therapy for neurodegenerative diseases has received a great deal of scientific and public interest in recent years. This is due to the remarkable pace at which paradigm-changing discoveries have been made regarding the neurogenic potential of embryonic, fetal, and adult cells. Over the last decade, clinical fetal tissue transplants have demonstrated that dopaminergic neurons can survive long term and provide functional clinical benefits for patients with Parkinson's disease. Pluripotent embryonic stem cells and multipotent neural stem cells may provide renewable sources that could replace these primary fetal grafts. Considerable advancement has been made in generating cultures with high numbers of neurons in general and of dopaminergic neurons using a varied array of techniques. However, much of this encouraging progress still remains to be tested on long-term expanded human cultures. Further problems include the low survival rate of these cells following transplantation and the tumorigenic tendencies of embryo-derived cells. However, pre-differentiation or genetic modification of stem cell cultures prior to transplantation may help lead to the generation of high numbers of cells of the desired phenotype following grafting. Boosting particular factors or substrates in the culture media may also protect grafted neurons from oxidative and metabolic stress, and provide epigenetic trophic support. Possible endogenous sources of cells for brain repair include the transdifferentiation of various types of adult cells into neurons. Despite the excitement generated by examples of this phenomenon, further work is needed in order to identify the precise instructive cues that generate neural cells from many other tissue types, and whether or not the new cells are functionally normal. Furthermore, issues such as cell homogeneity and fusion need to be addressed further before the true potential of transdifferentiation can be known. Endogenous stem cells also reside in the neurogenic zones of the adult brain (ventricle lining and hippocampus). Further elucidation of the mechanisms that stimulate cell division and migration are required in order to learn how to amplify the small amount of new cells generated by the adult brain and to direct these cells to areas of injury or degeneration. Finally, a more fundamental understanding of brain injury and disease is required in order to circumvent local brain environmental restrictions on endogenous cell differentiation and survival.