Transforming growth factor-β1 inhibits the proliferation of rat astrocytes induced by serum and growth factors

A number of cytokines and growth factors may affect astrocyte proliferation and functions. Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine which exerts multiple effects on growth and differentiation of different cell types. TGF-β1 is present in low amounts in the normal brain. TGF-β1 gene expression, however, is increased in the central nervous system (CNS) in several pathological conditions. In this study we examined the in vitro effects of TGF-β1 on the proliferative response of rat astrocytes to serum and growth factors. Astrocyte cultures were established from the cerebellum and cortex of newborn Lewis rats. The proliferative response of these cultures to serum and growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), IGF-2, interleukin 1 (IL-1)] was studied by [³H]-thymidine incorporation test in the presence or absence of TGF-β1. TGF-β1 significantly inhibited the proliferative response of astrocyte cultures to both autologous and heterologous serum. In addition, a strong inhibition of bFGF-, EGF-, and PDGF-induced proliferation was observed. The effect of TGF-β1 on the proliferative response to IL-1 was less evident but still significant. No effect was observed when TGF-β1 was added to IGF-1 and IGF-2 stimulated cultures. These data confirm previous reports showing a down-regulating activity of TGF-β on astrocyte proliferation and suggest that this cytokine may play physiological and pharmacological roles in the regulation of reactive astrocytosis in the CNS. © 1995 Wiley-Liss, Inc.     

Axonal regeneration by chronically injured supraspinal neurons can be enhanced by exposure to insulin-like growth factor, basic fibroblast growth factor or transforming growth factor beta

To test whether known growth factors could promote the regenerative reponse of chronically injured neurons, we exposed the injured adult rat spinal cord to insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF) or transforming growth factor beta 1 + 2 (TGFβs) 1 month after creation of a hemisection lesion. At 1 week later an autologous peripheral nerve graft was apposed to the rostral cavity wall and 1 month later Nuclear Yellow (NY) was used to retrogradely label neurons that had grown an axon into the graft. Neurons capable of axonal regeneration after a long term (5 weeks) injury were double labeled with True Blue (TB, provided at the time of hemisection lesion) and NY. Exposure to any of the three growth factors, compared to a PBS-treated control, resulted in a significant increase in the total number of regenerating supraspinal neurons, with the greatest increase after treatment with TGFβs. Treatment with TGFβs or bFGF led to a significant increase in the number of regenerating neurons in 6 out of 7 major regions (excluding the motor cortex) contributing to descending spinal pathways. Treatment with IGF-1 promoted significant regeneration only by reticular formation neurons. These results indicate that exposure to specific growth factors can enhance axonal regeneration by chronically injured neurons, thus overcoming one significant challenge to the repair of long standing structural damage to the spinal cord. ? 1996 Elsevier Science Ireland Ltd. All rights reserved.     

TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice

Astrocytes respond to environmental cues and play a multifaceted role in the response to trauma in the central nervous system. As the most prevalent contributors to the glial scar, astrocytes are targeted as barriers to regeneration. However, there is also strong evidence that astrocytes are vital for neuroprotection and metabolic support after injury. In addition, consistent with their role during development, astrocytes may be capable of supporting the growth of injured axons. Therefore, we hypothesized that with appropriate stimulation, the reparative functions of endogenous astrocytes could be harnessed to promote axon growth and recovery after spinal cord injury. Transforming growth factor-α (TGF-α) is a mitogenic growth factor that is active on astrocytes and is poised to contribute to such a strategy. Recombinant TGF-α was administered intrathecally to adult C57BL/6 mice for two weeks following a moderate mid-thoracic spinal cord contusion. By three weeks post-injury, TGF-α infusion had not affected locomotor recovery, but promoted extensive axon growth and altered the composition of the lesion site. The center of the lesion in the treated mice contained greater numbers of new cells and increased astrocyte invasion. Despite the expression of inhibitory proteoglycans, there was a marked increase in axons expressing neurofilament and GAP-43 immunoreactivity, and the new axons were closely associated with increased laminin expression within and beyond the astrocyte matrix. The results demonstrate that astrocytes are dynamic players in the response to spinal cord injury, and the growth-supportive role of these cells can be enhanced by TGF-α infusion.     

损伤神经周围注射自体PRP对周围神经损伤的修复效果观察

目的 探讨损伤神经周围注射自体富血小板血浆(platelet-rich plasma,PRP)对周围神经损伤的修复效果。方法 选取2017年1月-2018年7月于本院接受治疗的周围神经损伤患者130例,随机分为手术组、PRP联合组各65例,手术组患者进行显微外科手术,PRP联合组患者在手术基础上注射自体PRP进行治疗; 用酶联免疫吸附实验法检测血清C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平,用Western blot法检测胰岛素样生长因子1(IGF-1)、血管内皮生长因子(VEGF)表达水平,并对2组患者神经传导速度、下肢运动功能、基本功能优良率以及肌电图疗效进行检测。结果 治疗1、3、6、12个月后PRP联合组患者CRP、TNF-α水平均低于手术组,IGF-1、VEGF表达水平均高于手术组(P<0.05); 治疗1、3、6、12个月后PRP联合组患者感觉、运动神经传导速度、下肢运动功能评分、基本功能恢复优良率、肌电图愈显率均高于手术组(P<0.05)。结论 在手术治疗的基础上注射自体PRP对周围神经损伤患者进行治疗,能够减轻患者炎性损伤程度,上调IGF-1、VEGF的表达水平,加快神经传导速度,促进患者下肢运动功能恢复     

阿托伐他汀对EAE大鼠脊髓ICAM-1和TGF-β1表达的影响

目的 探讨阿托伐他汀对实验性自身免疫性脑脊髓炎(EAE)大鼠脊髓细胞间黏附分子-1(ICAM-1)和转化生长因子-β1(TGF-β1)表达的影响. 方法 80只清洁级健康雌性Wistar大鼠按照随机数字表法分为4组:正常对照组、EAE模型组、低剂量治疗组、高剂量治疗组,每组20只.各组再分为第14天、21天两个亚组,每个亚组10只.利用新鲜豚鼠全脊髓匀浆及完全福氏佐剂免疫Wistar大鼠建立EAE模型.低、高剂量治疗组大鼠分别给予2 mg/(kg·d)、10 mg/(kg·d)阿托伐他汀灌胃,正常对照组及EAE模型组应用生理盐水灌胃.观察每组大鼠发病情况并进行神经功能障碍评分,采用HE染色方法观察病理改变,免疫组化方法检测ICAM-1及TGF-β1的表达. 结果 与EAE模型组及低剂量治疗组比较,阿托伐他汀高剂量治疗组发病率明显减轻,炎性病灶明显减少,组织中ICAM-1表达明显减少,TGF-β1表达明显增多,差异均有统计学意义(P＜0.05).结论 阿托伐他汀可改善EAE大鼠的临床症状及病理改变,并且与剂量有关,其作用推测与减少ICAM-1表达、提高TGF-β1表达有关.     

Transforming growth factor beta expression in reactive spinal cord microglia and meningeal inflammatory cells during experimental allergic neuritis

Experimental allergic neurities (EAN), an inflammatory demyelinating disorder of the peripheral nervous system, is preceded and accompanied by a massive microglial reaction in the spinal cord which occurs in the absence of inflammatory cells infiltrating the cord parenchyma. Since transforming growth factor beta (TGF-β) has been shown to play a beneficial role in experimental autoimmune disease and might be involved in the regulation of glial activity, we have investigated the expression of TGF-β in EAN spinal cord and nerve root tissue. Adoptive transfer EAN was induced by the injection of neurotogenic T-cells specific for the P₂ myelin protein. In normal spinal cord tissue, both TGF-β1 and TGF-β3 mRNA were constitutively expressed at low levels. Already 3 days following injection of P₂-specific T-cells, TGF-β1 mRNA levels began to increase, peaked at day 6 at levels about tenfold above normal, and thereafter declined. TGF-β3 was induced even earlier with a sharp rise at day 3 and a peak fourfold above normal at day 4. In situ hybridization for TGF-β1 performed on spinal cord sections 6 days after injection of cells localized TGF-β1 mRNA to many nonneuronal cells with the typical morphology of microglia. In addition, TGF-β1 mRNA was observed in the meninges, and massive accumulation of signal was seen over inflammatory cells infiltrating the nerve roots. Our data indicate that TGF-β1 and -β3 are involved in regulating the glial response in EAN and that activated microglial cells might control their own activity state by expressing TGF-β1. The expression of TGF-β1 by infiltrating inflammatory cells in the nerve roots might represent an important endogenous mechanism to limit the extent of inflammation. © 1993 Wiley-Liss, Inc.     

Anti-fibroblast growth factor-2 antibodies attenuate mechanical allodynia in a rat model of neuropathic pain

Peripheral nerve injury leads to the activation of spinal cord astrocytes, which contribute to maintaining neuropathic (NP) pain behavior. Fibroblast growth factor-2 (FGF-2), a neurotrophic and gliogenic factor, is upregulated by spinal cord astrocytes in response to ligation of spinal nerves L5 and L6 (spinal nerve ligation [SpNL]). To evaluate the contribution of spinal astroglial FGF-2 to mechanical allodynia following SpNL, neutralizing antibodies to FGF-2 were injected intrathecally. Administration of 18 microg of anti-FGF-2 antibodies attenuated mechanical allodynia at day 21 after SpNL and reduced FGF-2 and glial acidic fibrillary protein mRNA expression and immunoreactivity in the L5 spinal cord segment of rats with SpNL. These results suggest that endogenous astroglial FGF-2 contributes to maintaining NP tactile allodynia associated with reactivity of spinal cord astrocytes and that inhibition of spinal FGF-2 ameliorates NP pain signs.     

Effects of hypoxia on glial cell expression of angiogenesis-regulating factors VEGF and TGF-β

Perivascular glial cells are thought to be involved in physiologic vascularization and also in pathologic angiogenesis in the central nervous system. We have previously shown that astrocytes are a source of transforming growth factor-β (TGF-β) and another inhibiting factor, which block endothelial cell growth and induce their apoptosis. Astroglia are also known to express vascular endothelial growth factor (VEGF), which is up-regulated during hypoxia. Here we demonstrate the effects of hypoxia on the expression of both TGF-β and VEGF by retinal glial cells. Muller cells isolated from rat retina were incubated under hypoxia or normoxia and the resulting conditioned media (H-MCM and N-MCM) were assayed for their effects on growth of bovine retinal capillary endothelial (BRE) and the TGF-β-sensitive mink lung epithelial CCL cells. The expression and quantities of VEGF and TGF-β (active vs. latent form) were determined by immuno-adsorption, Western or Northern blotting, and ELISA. N-MCM stimulated BRE cell growth by twofold but inhibited CCL cells under similar assay conditions, whereas H-MCM had a weak stimulating effect on BRE and substantial inhibitory activity on CCL cells. Adsorption of MCM by specific antibodies as well as Western and Northern blot analysis indicated that stimulating and inhibitory activities of MCM are due to the presence of VEGF and TGF-β, respectively. ELISA revealed that the hypoxia condition converts latent TGF-β into its active form. In N-MCM, TGF-β is found predominantly in the latent form, but in hypoxia MCM it is mainly active. Furthermore, it was found that treatment of Muller cells with exogenous TGF-β under either hypoxia or normoxia increases VEGF expression in a time- and dose-dependent fashion. TGF-β activation may, therefore, be prerequisite for hypoxia-induced up-regulation of VEGF and stimulation of angiogenesis in vivo. GLIA 24:216–225, 1998. © 1998 Wiley-Liss, Inc.     

Insulin-like growth factor-1 receptors in human spinal cord: changes in amyotrophic lateral sclerosis

Summary Neurotrophic factors are important for neuronal survival and maintenance in the adult nervous system. The regional distribution of insulin-like growth factor-1 (IGF-1) receptors in human spinal cords from controls and amyotrophic lateral sclerosis (ALS) patients was studied by immunohistochemistry and quantitative autoradiography. When comparing¹²⁵I-IGF-1 binding in the different spinal levels of normal spinal cord the same distribution pattern was found in which the binding was highest in the central canal > dorsal horn > ventral horn > white matter. In the ALS cases although a general upregulation of IGF-1 receptors was observed throughout the spinal cord, significant increases were observed in the cervical and sacral segments compared to controls. IGF-1 receptor immunoreactivity showed a similar pattern to that for¹²⁵I-IGF-1 binding, with immunoreactivity being found in the gray matter of the spinal cord and enhanced immunoreactivity occuring in ALS patients compared to controls. In agreement with the distribution of IGF-1 receptors, IGF-1 immunoreactivity was found within the gray matter of the spinal cord. The cartography of IGF-1 receptors in the normal spinal cord as well as the change of these receptors in diseased spinal cord may be of importance in future treatment strategies of ALS.     

The role of thrombospondin-1 and transforming growth factor-β after spinal cord injury in the rat

Spinal cord injury (SCI) continues to result in high morbidity and mortality throughout the world. An effective neuroprotective agent is still not available to counteract secondary damage caused by traumatic injury. Thrombospondin-1 (TSP-1) and transforming growth factor-β (TGF-β) have a role in angiogenesis, scar deposition, inflammation and may affect astrocyte phenotype and mobility. We investigated the role of TSP-1 and TGF-β in a model of spinal cord injury in rats. Forty female Sprague-Dawley rats were randomly divided into two equal groups: the experimental group was subject to SCI using an impactor and the sham-operated group was not subject to SCI. These animals were sacrificed at 12 h and 24 h after SCI for immunochemistry and Western blot analysis of the injured spinal segment for the expression of the TSP-1 and TGF-β proteins. We found that TSP-1 and TGF-β expression increased immediately after SCI in the injured segment. After 12 h, TSP-1 concentrations increased more rapidly and dramatically than TGF-β in the injured segment of the spinal cord. Elevations in TSP-1 and TGF-β concentrations persisted for 24 h after injury. These results show that elevated expression of TSP-1 and TGF-β can be detected in the injured segment of the spinal cord 12 and 24 h after injury. Thus, TSP-1 and TGF-β may have a role in SCI.     

β淀粉样蛋白与生长因子变化与老年性痴呆致病因素的研究

目的：检测血清β淀粉样蛋白（β－ＡＰ）和多肽生长因子含量变化,探讨其在Ａｌｚｈｅｉｍｅｒ病（ＡＤ）和血管性痴呆（ＶＤ）发病机制中的可能作用。方法：采用放射免疫分析法（ＲＩＡ）检测临床诊断为ＡＤ患者８例,ＶＤ患者１５例及６３例缺血性脑血管病（ＩＣＶＤ）患者血清β－ＡＰ、转化生长因子α（ＴＧＦ－α）和类胰岛素样生长因子Ⅱ（ＩＧＦ－Ⅱ）的水平,同时与健康对照组比较。结果：ＡＤ与ＶＤ患者β－ＡＰ、ＴＧＦ－α和ＩＧＦ－Ⅱ水平明显高于ＩＣＶＤ组和健康对照组,均具有显著性差异。ＩＣＶＤ患者血清β－ＡＰ、ＴＧＦ－α和 ＩＧＦ－Ⅱ水平亦明显高于对照组,其中以脑梗塞后遗症（ＳＣＩ）和椎基底动脉供血不足（ＶＢＩ）组增高十分明显,与对照组比较差异显著（Ｐ＜０．０５）。ＡＤ与 ＶＤ患者 ３项测定指标之间具有明显的正相关。结论：①β－ＡＰ可能是ＡＤ和ＶＤ发病的危险因素。②引起ＡＤ和ＶＤ神经元毒性作用进而导致痴呆．这可能与ＴＧＦ－α和ＩＧＦ－Ⅱ增多有关。③β－ＡＰ与ＴＧＦ－α、ＩＧＦ－Ⅱ密切相关,在老年斑形成过程中可能起重要作用。     

Endogenous IGF-1 regulates the neuronal differentiation of adult stem cells

Stem cells from the adult forebrain of mice were stimulated to form clones in vitro using fibroblast growth factor-2 (FGF-2). At concentrations above 10 ng/ml of FGF-2, very few clones gave rise to neurons; however, if FGF-2 was removed after 5 days, 20-30% of clones subsequently gave rise to neurons. The number of neuron-containing clones and the number of neurons per clone was significantly enhanced, if insulin-like growth factor (IGF)-1 or heparin were added subsequent to FGF-2 removal. The spontaneous production of neurons after FGF-2 removal was shown to be due to endogenous IGF-1, since antibodies to IGF-1 and an IGF-1 binding protein totally inhibited neuronal production. Similarly, these reagents also abrogated the neuron-promoting effects of heparin. Thus, it appears that endogenous IGF-1 may be a major regulator of stem cell differentiation into neurons. Furthermore, it was found that high levels of IGF-1 or insulin promoted the maturation and affected the neurotransmitter phenotype of the neurons generated.     

An audit of immunohistochemical marker patterns in meningioma

Meningiomas may express a number of potentially growth-promoting receptors including receptors for progesterone, growth hormone and vascular endothelial growth factor (VEGF). These and other receptors are potential targets for chemotherapy. We have prospectively studied a panel of markers as a routine in order to obtain data of individual expression of markers that may provide targets for anti-receptor treatment. One hundred and seventy-five consecutive patients operated on for meningiomas between 2005 and 2008 were prospectively analysed with antibodies against receptors for growth hormone, insulin-like growth factor 1 (IGF-1), androgen receptors, progesterone receptors (PR) and antibodies against CD34, VEGF, Ki-67 and caspase-3. Expression of IGF-1 receptor (IGF-1r), epidermal growth factor receptor (EGFR) E30 and growth hormone receptor (GHr) was conserved across histological grades and found in 88% to 94% of meningiomas. PR were detected in 87%, but expression decreased in aggressive tumours. Angio-markers such as VEGF and CD34 were detected in 69% and 17% of meningiomas, respectively. Androgen receptors and caspase-3 were uncommon. The analyses of a panel were undertaken as a clinical routine in order to assess its feasibility and to provide data that can be utilised in a clinical setting. Three putative therapeutic receptor targets, IGF-1r, GHr and EGFR E30 were expressed in a large majority of tumours and in contrast to PR maintained expression despite increasing pathological grade of meningioma. Our data also suggest that anti-progesterone therapies and anti-angiogenic therapies could be targeted to subsets of meningioma patients who express PR or have CD34-positive tumours.     

Truncated IGF-1 exerts trophic effects on fetal brain tissue grafts

Truncated IGF-1 (tIGF-1), a form of IGF-1 identified in the human brain, has been suggested, from in vitro experiments, to exert neurotrophic effects on developing fetal brain tissue. We studied the effects of tIGF-1 and IGF-1 on small defined areas of the developing central nervous system by using the in vivo model of intraocular transplantation which allows for direct observations of graft survival and growth. Truncated IGF-1 was found to significantly enhance the growth of fetal spinal cord (Embryonic Day (E) 14) and parietal cortex (E16-17) grafts transplanted to the anterior chamber of the eye of adult rats. tIGF-1 increased the volume of cerebral cortex grafts by approximately 100% and of E14 spinal cord grafts by approximately 50%. E18 spinal cord grafts and hippocampal grafts were not stimulated by tIGF-1 as compared to controls given HSA. Effects in cortex were seen with tIGF-1 using concentrations down to at least 10 ng/microliters. Interestingly, intact IGF-1 had no effect on cortical grafts. These findings show for the first time, using an in vivo system, that tIGF-1 is a potent stimulator of growth of grafted fetal cortex cerebri and spinal cord and suggest a possible role for endogenous tIGF-1 in cortical and spinal cord development.     

IGF-1 stimulates de novo fatty acid biosynthesis by Schwann cells during myelination

Schwann cell (SC) differentiation to the myelinating phenotype is characterized by the elaboration of a lipid-rich membrane and the expression of myelin-specific proteins. Insulin-like growth factor-1 (IGF-1) has been identified as a growth factor that stimulates the early events of myelination in SCs that signals via the PI3K/Akt pathway. Given the role of IGF-1 in promoting myelination, we performed studies to determine if the fatty acid biosynthetic pathway was a target of IGF-1 signaling in the formation of myelin membrane in dorsal root ganglion neuron/Schwann cell (DRG/SC) cocultures. We report that the fatty acid profile of lipid extracts of cocultures treated with IGF-1 match that reported for native myelin membrane by electrospray mass spectroscopy analysis. We also demonstrate de novo fatty acid biosynthesis in response to IGF-1 treatment in DRG/SC cocultures metabolically labeled with (13)C-acetate as a carbon source for fatty acid synthesis. Consistent with this finding, Western blot analysis of lysates from both cocultures and purified SCs reveal that IGF-1 stimulates two key fatty acid synthesizing enzymes. Additionally, we show that stimulation of fatty acid synthesizing enzymes is mediated by the PI3K/Akt signaling pathway. We also show that the fatty acid synthesizing enzymes and associated signaling pathways are elevated during the period of myelin membrane formation in sciatic nerve. Collectively, these findings demonstrate that IGF-1 plays an important regulatory function during myelin membrane formation.     

IGF-1 and BDNF promote chick bulbospinal neurite outgrowth in vitro

Injured neurons in the CNS do not experience significant functional regeneration and so spinal cord insult often results in permanently compromised locomotor ability. The capability of a severed axon to re-grow is thought to depend on numerous factors, one of which is the decreased availability of neurotrophic factors. Application of trophic factors to axotomized neurons has been shown to enhance survival and neurite outgrowth. Although brainstem-spinal connections play a pivotal role in motor dysfunction after spinal cord injury, relatively little is known about the trophic sensitivity of these populations. This study explores the response of bulbospinal populations to various trophic factors. Several growth factors were initially examined for potential trophic effects on the projection neurons of the brainstem. Brain derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1) significantly enhance mean process length in both the vestibulospinal neurons and spinal projection neurons from the raphe nuclei. Nerve growth factor (NGF), neurotrophin-4 (NT-4) and glial derived neurotrophic factor (GDNF) did not effect process outgrowth in vestibulospinal neurons. At the developmental stages used in this study, it was determined that receptors for BDNF and IGF-1 were present both on bulbospinal neurons and on surrounding cells with a non-neuronal morphology.     

Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state

Axon regeneration after experimental spinal cord injury (SCI) can be promoted by combinatorial treatments that increase the intrinsic growth capacity of the damaged neurons and reduce environmental factors that inhibit axon growth. A prior peripheral nerve conditioning lesion is a well-established means of increasing the intrinsic growth state of sensory neurons whose axons project within the dorsal columns of the spinal cord. Combining such a prior peripheral nerve conditioning lesion with the infusion of antibodies that neutralize the growth inhibitory effects of the NG2 chondroitin sulfate proteoglycan promotes sensory axon growth through the glial scar and into the white matter of the dorsal columns. The physiological properties of these regenerated axons, particularly in the chronic SCI phase, have not been established. Here we examined the functional status of regenerated sensory afferents in the dorsal columns after SCI. Six months post-injury, we located and electrically mapped functional sensory axons that had regenerated beyond the injury site. The regenerated axons had reduced conduction velocity, decreased frequency-following ability, and increasing latency to repetitive stimuli. Many of the axons that had regenerated into the dorsal columns rostral to the injury site were chronically demyelinated. These results demonstrate that regenerated sensory axons remain in a chronic pathophysiological state and emphasize the need to restore normal conduction properties to regenerated axons after spinal cord injury.     

The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate

Amyotrophic lateral sclerosis (ALS) is caused by motor neuron death. The relationship between the prognosis of ALS patients and the function of their bone marrow mesenchymal stromal cells (BM-MSCs) is unclear. We designed this study to assess the correlation between the progression rate of the ALS Functional Rating Scale-revised version (ΔFS), which is reported to predict prognosis, and the pluripotency and trophic factor secreting capacity of ALS patients' BM-MSCs. We evaluated ΔFS in 23 ALS patients and isolated BM-MSCs from those patients and five healthy people. Levels of Nanog, Oct-4, and Nestin mRNA were examined to evaluate pluripotency, and levels of BDNF, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF-1α, GDNF, VEGF, and ANG mRNA were examined to assess trophic factor secreting capacity. In addition, we measured the protein levels of Nanog, Oct-4, Nestin, SDF-1α, ANG, bFGF-2, VEGF, IGF-1, GDNF, and BDNF. mRNA levels of Nanog, Oct-4, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF-1α, GDNF, VEGF, and ANG were negatively correlations with ΔFS. However, those of Nestin and BDNF were not significantly correlated with ΔFS. Similarly, Nanog, Oct-4, SDF-1α, ANG, bFGF-2, VEGF, IGF-1, and GDNF protein levels had a significant negative correlation with ΔFS. Results indicate that the pluripotency and trophic factor secreting capacity of the BM-MSCs of ALS patients are reduced in proportion to a poorer prognosis. We therefore suggest that healthy allogeneic BM-MSCs might be a better option for cell therapy in ALS patients.