scholarly journals Bone marrow-derived neural crest precursors improve nerve defect repair partially through secreted trophic factors

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haiyan Shi ◽  
Xiaoli Li ◽  
Junling Yang ◽  
Yahong Zhao ◽  
Chengbin Xue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Peripheral Nerve ◽  
Neural Crest ◽  
Sensory Neurons ◽  
Sensory Function ◽  
Trophic Factors ◽  
Factor Alpha ◽  
Bone Marrow Origin ◽  
Rat Bone

Abstract Background Emerging evidence suggests that neural crest-derived cells (NCCs) present important functions in peripheral nerve regeneration to correct the insufficiency of autogenous Schwann cells. Postmigratory NCCs have been successfully isolated from adult rat bone marrow in our previous work. In this study, we aim to provide neural crest-derived Schwann cell precursors (SCPs) for repair of nerve defects in adult rats, and partially reveal the mechanisms involved in neuroregeneration of cell therapy. Methods A clonal cell line of neural crest precursors of rat bone marrow origin (rBM-NCPs) with SCP identity was expanded in adherent monolayer culture to ensure the stable cell viability of NCPs and potentiate the repair of nerve defects after rBM-NCPs implantation based on tissue engineering nerve grafts (TENG). Here the behavioral, morphological, and electrophysiological detection was performed to evaluate the therapy efficacy. We further investigated the treatment with NCP-conditioned medium (NCP-CM) to sensory neurons after exposure to oxygen-glucose-deprivation (OGD) and partially compared the expression of trophic factor genes in rBM-NCPs with that in mesenchymal stem cells of bone marrow origin (rBM-MSCs). Results It was showed that the constructed TENG with rBM-NCPs loaded into silk fibroin fiber scaffolds/chitosan conduits repaired 10-mm long sciatic nerve defects more efficiently than conduits alone. The axonal regrowth, remyelination promoted the reinnervation of the denervated hind limb muscle and skin and thereby alleviated muscle atrophy and facilitated the rehabilitation of motor and sensory function. Moreover, it was demonstrated that treatment with NCP-CM could restore the cultured primary sensory neurons after OGD through trophic factors including epidermal growth factor (EGF), platelet-derived growth factor alpha (PDGFα), ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor alpha (VEGFα). Conclusions In summary, our findings indicated that monolayer-cultured rBM-NCPs cell-based therapy might effectively repair peripheral nerve defects partially through secreted trophic factors, which represented the secretome of rBM-NCPs differing from that of rBM-MSCs.

scholarly journals Serum-mediated Activation of Bone Marrow–derived Mesenchymal Stem Cells in Ischemic Stroke Patients

2018 ◽  
Vol 27 (3) ◽  
pp. 485-500 ◽  
Author(s):  
Gyeong Joon Moon ◽  
Yeon Hee Cho ◽  
Dong Hee Kim ◽  
Ji Hee Sung ◽  
Jeong Pyo Son ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Critical Role ◽  
Trophic Factors ◽  
Human Mscs ◽  
Stroke Patients ◽  
Serum Factors ◽  
Control Serum

Stroke induces complex and dynamic, local and systemic changes including inflammatory reactions, immune responses, and repair and recovery processes. Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. We hypothesized that serum factors play a critical role in the activation of bone marrow (BM) MSCs after stroke such as by increasing proliferation, paracrine effects, and rejuvenation. Human MSCs (hMSCs) were grown in fetal bovine serum (FBS), normal healthy control serum (NS), or stroke patient serum (SS). MSCs cultured in growth medium with 10% SS or NS exhibited higher proliferation indices than those cultured with FBS ( P < 0.01). FBS-, NS-, and SS-hMSCs showed differences in the expression of trophic factors; vascular endothelial growth factor, glial cell–derived neurotrophic factor, and fibroblast growth factor were densely expressed in samples cultured with SS ( P < 0.01). In addition, SS-MSCs revealed different cell cycle– or aging-associated messenger RNA expression in a later passage, and β-galactosidase staining showed the senescence of MSCs observed during culture expansion was lower in MSCs cultured with SS than those cultured with NS or FBS ( P < 0.01). Several proteins related to the activity of receptors, growth factors, and cytokines were more prevalent in the serum of stroke patients than in that of normal subjects. Neurogenesis and angiogenesis were markedly increased in rats that had received SS-MSCs ( P < 0.05), and these rats showed significant behavioral improvements ( P < 0.01). Our results indicate that stroke induces a process of recovery via the activation of MSCs. Culture methods for MSCs using SS obtained during the acute phase of a stroke could constitute a novel MSC activation method that is feasible and efficient for the neurorestoration of stroke.

scholarly journals Human and Rat Bone Marrow-Derived Mesenchymal Stem Cells Differ in Their Response to Fibroblast Growth Factor and Platelet-Derived Growth Factor

2018 ◽  
Vol 24 (23-24) ◽  
pp. 1831-1843
Author(s):  
Donald Lennon ◽  
Luis A. Solchaga ◽  
Rodrigo A. Somoza ◽  
Mark D. Schluchter ◽  
Seunghee Margevicius ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Fibroblast Growth ◽  
Rat Bone

scholarly journals Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2385-2392 ◽  
Author(s):  
TM Walz ◽  
C Malm ◽  
BK Nishikawa ◽  
A Wasteson
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Transforming Growth Factor Alpha ◽  
Epidermal Growth ◽  
Factor Alpha

The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.

scholarly journals Differences and Similarities in the Neurotrophic Growth Factor Requirements of Sensory Neurons Derived from Neural Crest and Neural Placode

1985 ◽  
Vol 1985 (Supplement 3) ◽  
pp. 115-129 ◽  
Author(s):  
R. M. LINDSAY ◽  
Y.-A. BARDE ◽  
A. M. DAVIES ◽  
H. ROHRER
Keyword(s):  
Growth Factor ◽  
Neural Crest ◽  
Sensory Neurons

Differentiation of Mesenchymal Stem Cells from Rat Bone Marrow into Dopaminergic Neuron-Like Cells In Vitro.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4067-4067
Author(s):  
Li Chen ◽  
Dongmei He ◽  
Yuan Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Dopaminergic Neuron ◽  
Bone Marrow Mscs ◽  
Rt Pcr ◽  
Promising Source ◽  
Rat Bone

Abstract Mesenchymal stem cells (MSC) from bone marrow cavity are multipotent cells. Their primary function is to support the growth and differentiation of hematologic progenitors. MSCs have been shown to differentiate into a variety of cell types including: bone, adipocytes, cartilage, neuron-like, and muscle-like cells. This project aimed to induce MSCs from rat bone marrow into mature dopamine secreting cells. MSCs were isolated from rat bone marrow, cultured and passaged. After propagating for three generations in vitro culture, MSCs were induced by epidermal growth factor, basic fibroblast growth factor and retinoic acid. After induction, morphologic change was examined by light microscope. NSE,MAP-2a, b and tyrosine hydroxylase (TH) was examined by immunocytochemistry. The related genes of the differentiated neurons, such as Nurr-1, nestin, mash-1,DR2-L,AADC and TH were detected by RT-PCR. After MSCs were inducted for 7 days,14 days and 21 days, dopamine production and release in the extract and medium of dopaminergic-induced cultured cells was assayed by dopamine ELISA. After 14 days of induction, MSC showed neuron-like morphologic changes and expressed NSE, MAP-2a, b and TH. RT-PCR. showed that these induced cells expressed nerves stem cells gene Nestin,Nurr-1 and dopamine nerves gene mash-1,DR2-L,AADC,TH. Most importantly, dopamine ELISA analysis showed the evidence of dopamine release in the extract and medium of dopaminergic-induced clonal MSCs. The results suggest that bone marrow MSCs from rat can be induced to differentiate into dopaminergic neuron-like cells in vitro. Bone marrow MSCs will provide a promising source of neural progenitor cells and may be a favorable candidate for cellular therapy of Parkinson’s disease.

Effect of rat bone marrow stromal stem cells overexpressing platelet-derived growth factor and bone morphogenic protein into platelet-rich plasma gels on osteogenic differentiation

2020 ◽  
Vol 10 (7) ◽  
pp. 1068-1078
Author(s):  
Jin Sun ◽  
Xin Jiang ◽  
Weilian Chen ◽  
Weikun Zheng ◽  
Junhao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Growth Factor ◽  
Osteogenic Differentiation ◽  
Platelet Rich Plasma ◽  
Genetically Modified ◽  
Bone Morphogenic Protein ◽  
Platelet Derived Growth Factor ◽  
Stromal Stem Cells ◽  
Rat Bone

The aim of this study was to improve osteoblast function by incorporating rat bone marrow stromal stem cells (rBMSCs) overexpressing platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) into platelet-rich plasma (PRP) gels. rBMSCs were isolated, cultured, and identified. The rBMSCs were subsequently co-transfected with two recombinant adenoviruses delivering PDGF-BB-GFP and BMP-2-GFP. PDGF-BB and BMP-2 expression levels in transduced BMSCs were detected, and a post-transfection analysis of the osteogenic differentiation trend of rBMSCs was performed. Autologous PRP gels were constructed and optimized, and the levels of growth factor in PRP were detected. The optimal growth conditions of the genetically-modified rBMSCs in the scaffolds were established, and the effects of tissue engineering materials and PRP gel construction on the osteogenic differentiation of rBMSCs were assessed. The results revealed that high-purity rBMSCs were obtained, and high levels of BMP-2 and PDGF-BB were secreted by the transduced cells. Furthermore, PRP promoted the proliferation and osteogenic differentiation of rBMSCs overexpressing PDGF-BB and BMP-2. Collectively, the results of the present study revealed that genetically modified rBMSCs incorporated into PRP gels enhanced osteogenic differentiation.

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