Neural Stem-Like Cells Derived from Human Amnion Tissue are Effective in Treating Traumatic Brain Injury in Rat

Although human amnion derived mesenchymal stem cells (AMSC) are a promising source of stem cells, their therapeutic potential for traumatic brain injury (TBI) has not been widely investigated. In this study, we evaluated the therapeutic potential of AMSC using a rat TBI model. AMSC were isolated from human amniotic membrane and characterized by flow cytometry. After induction, AMSC differentiated in vitro into neural stem-like cells (AM-NSC) that expressed higher levels of the neural stem cell markers, nestin, sox2 and musashi, in comparison to undifferentiated AMSC. Interestingly, the neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), glial cell derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were markedly upregulated after neural stem cell induction. Following transplantation in a rat TBI model, significant improvements in neurological function, brain tissue morphology, and higher levels of BDNF, NGF, NT-3, GDNF and CNTF, were observed in the AM-NSC group compared with the AMSC and Matrigel groups. However, few grafted cells survived with minimal differentiation into neural-like cells. Together, our results suggest that transplantation of AM-NSC promotes functional rehabilitation of rats with TBI, with enhanced expression of neurotrophic factors a likely mechanistic pathway.     

The functional study of human umbilical cord mesenchymal stem cells harbouring angiotensin‐converting enzyme 2 in rat acute lung ischemia‐reperfusion injury model

Acute lung ischemia‐reperfusion injury (ALIRI) is featured as non‐specific alveolar damage, lung edema and hypoxemia, often occurring within 72 h after surgery. It is the leading cause for primary graft failure and mortality after lung surgery and transplantation. Here we aimed to find a more effective therapeutic approach to treat ALIRI. We evaluated the combinational effects of human umbilical cord mesenchymal stem cells (HUMSCs) and angiotensin‐converting enzyme 2 (ACE2) in the rat ALIRI model. HUMSCs were isolated for lentiviral‐ACE2 transfection. Fifty rats were randomly divided into five groups: sham surgery, physiological saline (PS), ACE2, HUMSCs and HUMSCs‐ACE2 group. Several physiological, biochemical and histological indicators were examined and compared among the five groups, such as blood oxygen saturation (Sat O₂%) and right ventricular systolic blood pressure (RVSBP), pulmonary morphology observations, several kinds of cell markers and the abundance of glutathione reductase (GR), glutathione peroxidase (GPX) and NAD(P)H quinone oxidoreductase (NQO1). Compared with HUMSCs and ACE2 groups, HUMSCs‐ACE2 group showed lighter lung injuries, higher CD31 and vWF expression (endothelial cell surface markers), lower γ‐H2AX (DNA damage marker) and CD68 (inflammatory cell marker) and higher anti‐oxidants expression (GR, GPX and NQO1). The results indicated that HUMSCs harbouring ACE2 were more effective than either HUMSCs or ACE2 alone in alleviating the ALIRI damages. The synergistic effects of HUMSCs and ACE2 provide informative clues for mechanism study and therapeutic method development of ALIRI. Copyright © 2014 John Wiley & Sons, Ltd.     

Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord

Background

Human umbilical mesenchymal stem cells (HUMSCs) isolated from Wharton''s jelly of the umbilical cord can be easily obtained and processed compared with embryonic or bone marrow stem cells. These cells may be a valuable source in the repair of spinal cord injury.

Methodology/Principal Findings

We examine the effects of HUMSC transplantation after complete spinal cord transection in rats. Approximately 5×10⁵ HUMSCs were transplanted into the lesion site. Three groups of rats were implanted with either untreated HUMSCs (referred to as the stem cell group), or HUMSCs treated with neuronal conditioned medium (NCM) for either three days or six days (referred to as NCM-3 and NCM-6 days, respectively). The control group received no HUMSCs in the transected spinal cord. Three weeks after transplantation, significant improvements in locomotion were observed in all the three groups receiving HUMSCs (stem cell, NCM-3 and NCM-6 days groups). This recovery was accompanied by increased numbers of regenerated axons in the corticospinal tract and neurofilament-positive fibers around the lesion site. There were fewer microglia and reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the stem cell group than in the control group. Transplanted HUMSCs survived for 16 weeks and produced large amounts of human neutrophil-activating protein-2, neurotrophin-3, basic fibroblast growth factor, glucocorticoid induced tumor necrosis factor receptor, and vascular endothelial growth factor receptor 3 in the host spinal cord, which may help spinal cord repair.

Conclusions/Significance

Transplantation of HUMSCs is beneficial to wound healing after spinal cord injury in rats.     

Cografted Wharton’s Jelly Cells-derived Neurospheres and BDNF Promote Functional Recovery After Rat Spinal Cord Transection

An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted human umbilical mesenchymal stem cells-derived neurospheres (HUMSC-NSs) and BDNF can promote morphologic and functional recoveries of injured spinal cord. In vitro, HUMSC-NSs terminally differentiated into higher percentages of cells expressing neuronal markers: β-tubulin III and MAP2ab by the supplement with BDNF. Following grafted into injured spinal cord, very few grafted cells survived in the HUMSC-NSs + BDNF-treated (<3%) and HUMSC-NSs-treated (<1%) groups. The survived cells were differentiated into various cells, which were confirmed by double staining of BrdU and neural or glia markers. In comparison, more grafted cells in the HUMSC-NSs + BDNF group transformed into mature neural-like cells, while more grafted cells in the HUMSC-NSs group transformed into oligodendrocyte-like cells. HUMSC-NSs + BDNF-treated group had more greatly improved BBB scores, compared with HUMSC-NSs-treated and medium-treated groups. Additionally, axonal regeneration showed significant improvement in rats receiving HUMSC-NSs + BDNF, compared with HUMSC-NSs-treated and medium-treated groups, as demonstrated by the NF-200-positive staining and Fluorogold (FG) retrograde tracing study. Lastly, a significant reduction in the percentage cavitation was seen in the two cell-treated groups compared with medium control group. These results means BDNF could promote the neural differentiation of HUMSC-NSs in vitro and in vivo. However, cellular replacement is unlikely to explain the improvement in functional outcome. The functional recovery might more rely on the axonal regeneration and neuroprotective action that active by the grafted cells. Cografted HUMSCs and BDNF is a potential therapy for SCI.     

Human Umbilical Cord-Derived Schwann-Like Cell Transplantation Combined with Neurotrophin-3 Administration in Dyskinesia of Rats with Spinal Cord Injury

Mesenchymal stem cells are capable of differentiating into Schwann-like cells. In this study, we induced human umbilical-cord mesenchymal stem cells (HUMSCs) in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with Schwann-like cells. These HUMSC-derived Schwann-like cells, after grafting into the injured area of the rats’ spinal cord injury (SCI), showed a partial therapeutic effect in terms of improving the motor function. Neurotrophin-3 (NT-3) was reported to improve the local microenvironment of the grafted cells, and we, therefore, further tested the effect of Schwann-like cell grafting combined with NT-3 administration at the site of cell transplantation. The results showed that NT-3 administration significantly promoted the survival of the grafted cells in the host-injured area. Significant improvement in rats treated by Schwann-like cell grafting combined with NT-3 administration was demonstrated in the behavioral test as compared with that in animal models received the cell grafting only. These results suggest that transplantation of the Schwann-like cells combined with NT-3 administration may represent a new strategy of stem cell therapy for spinal cord injury.     

In Vitro and In Vivo Magnetic Resonance Tracking of Sinerem-Labeled Human Umbilical Mesenchymal Stromal Cell-Derived Schwann Cells

Tracking of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles-labeled embryonic stem cells, neural stem cells, or adult mesenchymal stem cells in vitro and in vivo by using magnetic resonance (MR) imaging have been reported. However, whether the transdifferentiated cells can be effectively labeled by USPIO has not yet been investigated. The requirement for nerve donor material evokes additional morbidity and inability to generate a sufficiently large number of cells in a short time to hamper the clinic application of Schwann cells (SCs) transplantation. These limitations may be avoided if SCs can be generated from clinically accessible sources, such as bone marrow and umbilical cord. However, a reliable means of inducing the selective differentiation of human mesenchymal stromal cells isolated from the umbilical cord (HUMSCs) into SCs in vitro has not yet been established. In this study, we induce HUMSCs into Schwann-like cells in terms of morphology, phenotype, and function by an improved protocol basing on our previous studies. Furthermore, HUMSCs-derived SCs are labeled efficiently in vitro with ultrasmall superparamagnetic iron oxide contrast agent (USPIO) Sinerem and poly-l-lysine (PLL) without affecting morphology, cell cycle, proliferation, and differentiation ability of the labeled cells between the concentration of 200 to 800 μg/ml. Importantly, when grafted into the intact cerebral cortex and striatum, the survival and migration of these Sinerem-labeled cells were observed using MRI. Our study suggest the effective concentration field for Sinerem use in tracking transdifferentiated HUMSCs, and Sinerem labeling transdifferentiated HUMSCs is feasible, efficient, and safe for MRI tracing following grafting into nervous system.     

Human umbilical cord mesenchymal stem cell transplantation restores damaged ovaries

Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane‐labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury.     

Differentiation of human umbilical cord Wharton's jelly‐derived mesenchymal stem cells into germ‐like cells in vitro

Recent studies have demonstrated that mesenchymal stem cells could differentiate into germ cells under appropriate conditions. We sought to determine whether human umbilical cord Wharton's jelly‐derived mesenchymal stem cells (HUMSCs) could form germ cells in vitro. HUMSCs were induced to differentiate into germ cells in all‐trans retinoic acid, testosterone and testicular‐cell‐conditioned medium prepared from newborn male mouse testes. HUMSCs formed “tadpole‐like” cells after induction with different reagents and showed both mRNA and protein expression of germ‐cell‐specific markers Oct4 (POUF5), Ckit, CD49_f (α6), Stella (DDPA3), and Vasa (DDX4). Our results may provide a new route for reproductive therapy involving HUMSCs and a novel in vitro model to investigate the molecular mechanisms that regulate the development of the mammalian germ lineage. J. Cell. Biochem. 109: 747–754, 2010. © 2010 Wiley‐Liss, Inc.     

人羊膜间充质干细胞对四氯化碳诱导小鼠肝损伤定位修复的研究

目的：观察活体染料羧基荧光素乙酰乙酸（CFSE）标记的人羊膜间充质干细胞对四氯化碳诱导小鼠肝损伤模型的定位修复情况。方法：采用胰蛋白酶-胶原酶消化法从羊膜组织中分离间充质干细胞,通过流式细胞术和免疫荧光等方法进行鉴定。模型组按浓度为20μl/g剂量的四氯化碳和橄榄油混合液诱导小鼠肝损伤,治疗组经小鼠尾静脉注射羧基荧光素乙酰乙酸标记的人羊膜间充质干细胞约1×10⁶个/ml。分别取模型组和细胞移植的治疗组小鼠眼球血和肝组织进行相关检测。结果：分离得到纯度较高的羊膜间充质干细胞;冰冻切片免疫荧光显示移植1周后细胞向小鼠受损肝组织定植,CFSE标记的人羊膜间充质干细胞呈绿色荧光;细胞移植后4周,与模型组比较,细胞移植组小鼠血清中天冬氨酸转移酶、丙氨酸氨基转移酶显著降低,而白蛋白明显升高（P< 0.01）;肝组织病理切片模型组小鼠细胞水肿,坏死灶多见,脂肪变性,可见不同程度的炎性细胞浸润;治疗组小鼠肝组织病理学改变和损伤程度有较明显改善;小鼠肝组织冰冻切片的免疫荧光显示移植4周后人羊膜间充质干细胞周围分泌血清白蛋白。结论：羧基荧光素乙酰乙酸标记的人羊膜间充质干细胞可有效改善肝组织的生理功能,为细胞定位移植治疗肝脏疾病的修复情况提供实验数据。     

Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.     

Is the subarachnoid administration of mesenchymal stromal cells a useful strategy to treat chronic brain damage?

Background aimsTraumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Developing effective protocols for the administration of mesenchymal stromal cells (MSCs) is a promising therapeutic strategy to treat TBI. It is important to develop alternatives to direct parenchymal injection at the injury site because direct injection is an expensive and invasive technique. Subarachnoid transplantation, a minimally invasive and low-risk procedure, may be an important and clinically applicable strategy. The aim of this study was to test the therapeutic effect of subarachnoid administration of MSCs on functional outcome 2 months after an experimental TBI in rats.MethodsTwo months after TBI, 30 female Wistar rats were divided into 3 groups (n = 10 in each group): sham, MSC (received 2 × 10⁶ MSCs) and saline (received only saline) groups. Neurological function, brain and spinal cords samples and cerebrospinal fluid were studied.ResultsNo significant differences were found in neurological evaluation and after histological analysis; differences in the expression of neurotrophins were present but were not statistically significant. MSCs survived in the host tissue, and some expressed neural markers.ConclusionsSimilar to direct parenchymal injections, transplanted MSCs survive, migrate to the injury cavity and differentiate into mature neural cell types for at least 6 months after engraftment. These results open the possibility that MSC administration through subarachnoid administration may be a treatment for the consequences of TBI. The transplantation technique and cell number should be adjusted to obtain functional outcome and neurotrophin production differences.     

Adipose-derived mesenchymal stem cells stereotactic transplantation alleviate brain edema from intracerebral hemorrhage

Adipose-derived mesenchymal stromal cells (ADSCs) exhibited high potential in tissue repair and regeneration, and it has been proved that ADSCs could protect brain cells from apoptosis and maintaining blood-brain barrier stability after cerebral vascular disease. In this study, we evaluated the therapeutic potential and mechanism of ADSCs stereotactic transplantation in intracerebral hemorrhage (ICH) mice model and hemin-treated astrocytes. Mice were divided into three groups: sham group, ICH + PBS group, and ICH + ADSC group. Mice in ICH + ADSC group received ADSCs cell suspension stereotactic transplantation into the area beside the bleeding region. Astrocytes were divided into three groups: control group, hemin group, and hemin + ADSC group. Astrocytes in hemin + ADSC group were cultured in ADSCs-astrocyte no-contact coculture system and treated with 30 μM hemin solution. The results showed that ADSCs stereotactic transplantation improved functional outcomes and reduced cell apoptosis after ICH. Moreover, ADSCs stereotactic transplantation could alleviate brain edema and inflammation and AQP4 protein expression contributed to the alleviation of brain edema. In addition, mitogen-activated protein kinase (MAPK) pathways, including p38/MAPK pathway and c-Jun N-terminal kinase pathway, were involved in AQP4 modulation by ADSCs transplantation in ICH. In conclusion, ADSCs transplantation could alleviate the nervous tissue injury, reduce cell apoptosis, and relieve brain edema in ICH. And the edema regulation effect of ADSCs transplantation is associated with inhibition of inflammation and AQP4 protein expression.     

Anti-inflammatory Effect of Mesenchymal Stromal Cell Transplantation and Quercetin Treatment in a Rat Model of Experimental Cerebral Ischemia

Here, we have investigated the synergistic effect of quercetin administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following middle cerebral artery occlusion in rat. Combining quercetin treatment with delayed transplantation of HUMSCs after local cerebral ischemia significantly (i) improved neurological functional recovery; (ii) reduced proinflammatory cytokines (interleukin(IL)-1β and IL-6), increased anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor-β1), and reduced ED-1 positive areas; (iii) inhibited cell apoptosis (caspase-3 expression); and (iv) improved the survival rate of HUMSCs in the injury site. Altogether, our results demonstrate that combined HUMSC transplantation and quercetin treatment is a potential strategy for reducing secondary damage and promoting functional recovery following cerebral ischemia.     

Mesenchymal-like progenitors derived from human embryonic stem cells promote recovery from acute kidney injury via paracrine actions

Background aimsThe engraftment of mesenchymal stem cells (MSCs) is reported to promote recovery of renal function in animal models of acute kidney injury (AKI). However, it is unknown whether mesenchymal-like progenitors (MPs) derived from human embryonic stem cells (hESCs) can mediate similar therapeutic effects. We investigated the responses of recipient renal tissue to engraftment of hESC-MPs and underlying mechanisms of these effects.MethodsWe measured blood urea nitrogen and creatinine levels of AKI mice with hESC-MPs transplantation and control mice. We performed renal morphology analysis by immunohistochemistry and electron microscopy to confirm the renoprotective effects of engrafted hESC-MPs. Proliferation, apoptosis and gene expression of tubular cells were also monitored by immunohistochemistry and real-time quantitative polymerase chain reaction to investigate the mechanisms that occurred.ResultsAfter transplantation of hESC-MPs into mice with cisplatin-induced AKI, improvements in renal function and recovery from tubular epithelial cell injury were observed. Engrafted hESC-MPs were localized to areas of injured kidney 5 days after cisplatin induction, where they promoted tubular cell proliferation and decreased kidney cell apoptosis. The beneficial effect was further confirmed by the capability of the engrafted cells to up-regulate renal gene expression of anti-inflammatory cytokines and pro-survival cytokines. Meanwhile, infusion of these cells reduced renal gene expression of pro-inflammatory cytokines and monocyte chemotactic protein-1, a chemokine that stimulates monocyte and macrophage infiltration.ConclusionsOur results show that infused hESC-MPs may promote recovery from AKI by regulating related cytokines.     

Mesenchymal cells from human amniotic fluid survive and migrate after transplantation into adult rat brain

Amniotic fluid has been recently suggested as an alternative source of mesenchymal stem cells. However, the fate of amniotic fluid-derived mesenchymal stem cells (AF-MSCs) after in vivo transplantation has yet to be determined. In the present study we explored whether human AF-MSCs could survive and migrate following transplantation into the striatum of normal and ischemic rat. We found that the grafted cells could survive and migrate towards multiple brain regions in the normal animals, while they moved towards the injured region in the ischemic rat. Double-immunostaining analyses showed that the implanted human AF-MSCs express markers for immature neurons (Doublecortin) at 10 days, and for astrocytes (GFAP) at 10, 30 and 90 after transplantation. This study provides the first evidence that human amniotic fluid contains cells having the potential to survive and integrate into adult rat brain tissue and, therefore, to function as effective stem cells for therapeutic strategies.     

人脐带间充质干细胞静脉输注小鼠的安全性

目的探讨C57／BL6J小鼠重复多次尾静脉输注人脐带间充质干细胞后的免疫反应和毒性。方法将SPF级别的32只C57／BL6J小鼠随机分为阴性对照组、细胞移植组,每组16只,雌雄各半,细胞移植组小鼠尾静脉注射分离培养的第5代人脐带间充质干细胞,一次5×10。／只,每周注射一次,连续注射4周;阴性对照组每次注射相同容积的PBS。注射后后观察小鼠的一般症状,末次注射后i周、4周进行血细胞计数、血生化、免疫反应指标、脏器质量测定和组织病理学检查。结果细胞移植组小鼠血细胞计数、血生化、脏器重量和脏器系数与对照组无显著性差异（P〉0．05）,脏器组织病理学在光镜下检查结果与对照组无形态学差别,以及免疫结果测定（T细胞亚群CD3＋、CD4＋、CD8＋及CD4＋／CD8＋）与对照组无显著性差异（P〉0．05）。结论人脐带间充质干细胞重复多次尾静脉输注C57／BL6J小鼠是安全可行的,对受者无明显免疫反应和毒副作用。     

Human Umbilical Mesenchymal Stem Cells-Seeded Bladder Acellular Matrix Grafts for Reconstruction of Bladder Defects in a Canine Model

Background

The goal of this study was to explore the feasibility of utilizing human umbilical mesenchymal stem cells (HUMSCs)-seeded Bladder acellular matrix graft (BAMG) for bladder reconstruction in a canine model.

Methodology/Principal Findings

HUMSCs were isolated from newborn umbilical cords and identified by flow cytometry. Partial cystectomy was performed in the experimental and control group. Bladder defects were repaired with HUMSCs-BAMG in the experimental group and repaired with unseeded-BAMG in control group. The implanted grafts were harvested after surgery. H&E and immunohistochemistry staining were performed to evaluate the regeneration of the bladder defect. Primary cultured HUMSCs displayed typical fibroblast morphology with spindle-shaped. Flow cytometry indicated that these cells were positive for CD105 (97.3%) and CD44 (99%), but negative for CD34 (2.8%), CD31 (2.1%), and CD45 (1.7%). Immunohistochemistry staining showed that a multilayered urothelium and well-developed smooth muscle were observed at 12 weeks in experiment group. In contrast, multilayered urothelial tissues were also observed at 12 weeks in group B, but well-developed smooth muscle bundles were observed.

Conclusions/Significance

Our preliminary results demonstrate that UMSC-seeded BAMGs are superior to unseeded BAMGs to promote the regeneration of bladder defects. Our findings indicated that HUMSCs may be a potential cell source for bladder tissue engineering.     

骨髓间充质干细胞经BDNF基因修饰后移植治疗大鼠半横断脊髓损伤的电生理研究

目的采用电生理的研究方法,观察脑源性神经营养因子(BDNF)基因修饰的骨髓间充质干细胞对脊髓损伤的修复作用。方法随机将大鼠分成3组:空白组10只(只切除椎板,暴露脊髓硬脊膜);SCI组10只;SCI术后细胞移植组10只;从以上三组大鼠随机抽取8只于细胞移植后1 d、7 d、14 d、21 d、30 d、60 d进行SEP(皮层体感诱发电位)、MEP(运动诱发电位)等电生理检测技术,并观察大鼠的运动评分恢复程度。结果细胞移植4d后,大鼠饮食和活动开始增加;后肢变化过程如下:损伤后1~4 d损伤侧后肢迟缓性瘫痪,拖地行走,损伤对侧后肢由损伤初期的运动减弱逐渐恢复,损伤后5~9 d损伤侧后肢痉挛性瘫痪;10~14 d损伤侧下肢恢复少量活动,损伤对侧后肢恢复至较损伤前稍弱的状态;15~21 d损伤侧后肢活动能力较之前有明显改善,至30 d损伤侧后肢活动能力及肌张力恢复程度最明显,30 d以后无更明显改善。免疫组化发现损伤处诱导标记的骨髓间充质干细胞存活,行为学观察发现细胞移植改善了损伤大鼠运动能力。结论骨髓间充质干细胞经BDNF基因修饰后可以促进脊髓损伤大鼠的神经再生及部分传导功能恢复。