Bone regeneration in a rabbit ulna defect model: use of allogeneic adipose-derivedstem cells with low immunogenicity

Tissue engineering provides new potential treatments for the repair of bone defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) represent an attractive cell source for therapeutic applications involving tissue engineering, although disadvantages, such as pain of harvest and low proliferation efficiency, are major limitations to the application of BMSCs in the clinic. Adipose-derived stem cells (ASCs) with their multilineage potential and satisfactory proliferation potential can be induced into the osteogenic lineage in vitro and can be anchored onto suitable scaffolds as seed cells to repair bone defects successfully in an autologous setting. Previous studies have indicated that both undifferentiated BMSCs and ASCs exhibit immunosuppression and immunoprivilege properties. We compare the immuno-function of undifferentiated and osteo-differentiated ASCs in vitro and explore the feasibility of applying allogeneic ASCs to the repair of ulnar bone defects in the rabbit model. Our study demonstrates that allogeneic osteogenic differentiated ASCs maintain low immunogenicity and negative immunomodulation. The allogeneic osteogenic differentiated ASCs combined with demineralized bone matrix successfully regenerate ulnar bone defects in rabbits without immunosuppressive therapies.     

Icariin accelerates cartilage defect repair by promoting chondrogenic differentiation of BMSCs under conditions of oxygen‐glucose deprivation

This study explored the role played by combined ICA and bone mesenchymal stem cells (BMSCs) in repairing rabbit knee cartilage defects. Firstly, rabbit BMSCs were isolated and used to construct an in vitro cellular model of oxygen‐glucose deprivation/reoxygenation (OGD/R). Subsequently, ICA processing, Alcian blue staining, immunofluorescence and Western blot studies were performed to evaluate the ability of BMSCs to display signs of chondrogenic differentiation. Furthermore, a rabbit knee cartilage injury model was established in vivo. International Cartilage Repair Society (ICRS) macroscopic evaluations, H&E, Alcian blue and EdU staining, as well as immunohistochemistry, were analysed cartilage repair and pathological condition of the knee cartilage tissue. Our in vitro results showed that ICA promoted the chondrogenic differentiation of BMSCs, as well as aggrecan (AGR), bone morphogenetic protein 2 (BMP2) and COL2A1 protein expression in BMSCs. In vivo experiments showed that rabbits in the BMSCs or ICA treatment group had higher ICRS scores and displayed a better restoration of cartilage‐like tissue and chondrocyte expression on the surface of their cartilage defects. In conclusion, ICA or BMSCs alone could repair rabbit knee cartilage damage, and combined treatment with ICA and BMSCs showed a better ability to repair rabbit knee cartilage damage.     

胎盘间充质干细胞的体外培养及其生物学特性研究

目的：探讨胎盘间充质干细胞（PMSCs）的体外分离和培养方法,建立稳定的PMSCs体外培养扩增体系。方法：将胎盘组织经胶原酶消化、密度梯度离心、贴壁筛选法分离,获得并培养人PMSCs,观察细胞形态及其超微结构;应用流式细胞术测定细胞周期及CD14、CD29、CD34、CD44、CD45的表达,研究其增殖和生长特性。结果：在体外培养条件下,人PMSCs贴壁生长,为成纤维细胞样,与骨髓间充质干细胞相似;CD14/CD34/CD45阴性,CD29/CD44阳性,核浆比大,细胞周期检测G0/G1期约占95%,具有原始细胞的特征。结论：体外获得的PMSCs形态单一、生长稳定、增殖能力较强,具有与骨髓间充质干细胞相似的细胞形态、表面标志。由于其来源方便、丰富,无伦理学限制,因此可进一步用于细胞治疗的研究。     

The bone-forming effects of HIF-1α-transduced BMSCs promote osseointegration with dental implant in canine mandible

The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore the oral function. Gene-transduced stem cells provide a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants with tissue engineering technology. Our previous studies have demonstrated that the hypoxia-inducible factor-1α (HIF-1α) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the function of HIF-1α was validated for the first time in a preclinical large animal canine model in term of its ability to promote new bone formation in defects around implants as well as the osseointegration between tissue-engineered bone and dental implants. A lentiviral vector was constructed with the constitutively active form of HIF-1α (cHIF). The ectopic bone formation was evaluated in nude mice. The therapeutic potential of HIF-1α-overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1α mediated canine BMSCs significantly promoted new bone formation both subcutaneously and in mesi-implant defects, including increased bone volume, bone mineral density, trabecular thickness, and trabecular bone volume fraction. Furthermore, osseointegration was significantly enhanced by HIF-1α-overexpressing canine BMSCs. This study provides an important experimental evidence in a preclinical large animal model concerning to the potential applications of HIF-1α in promoting new bone formation as well as the osseointegration of immediate implantation for oral function restoration.     

DDR2基因缺失对小鼠骨髓间充质干细胞生物学特性的影响

目的:骨髓间充质干细胞(Bone Mesenchymal Stem Cells,BMSCs)是骨再生工程中重要的种子细胞,它对骨组织缺损的修复有着良好的效果。但是BMSCs向成骨细胞分化并修复骨组织缺损是是由细胞外因子共同作用产生的结果。DDR2(Discoidin Domain Receptor 2)作为I型胶原的特异性受体在成骨细胞的分化中发挥重要的调节作用。而对于其在BMSCs向成骨细胞的分化过程中的所起到的作用还鲜有研究,对其作用机理尚不明确。因此我们希望通过分离、培养并鉴定比较DDR2基因缺失小鼠与野生型小鼠来源的骨髓间充质干细胞了解其生物学特性,为后续的实验奠定理论基础。方法:采用改良型的全骨髓贴壁细胞分离方法分离培养两种小鼠来源的骨髓间充质干细胞,采用流式细胞技术鉴定其表面标记物的表达,并利用诱导培养液诱导骨髓间充质干细胞向成骨细胞和成脂肪细胞分化。结果:分离培养的两种骨髓间充质干细胞形态一致,增殖能力和自我更新能力强,流式细胞术检测其表面标记物CD29,Sca-1均表达阳性,CD105,CD45表达为阴性,分离得到的两种细胞均有向成骨细胞和成脂肪细胞分化的能力,但可以明显观察到DDR2基因缺失小鼠的骨髓间充质干细胞的成骨分化能力减弱。结论:本实验通过对于DDR2基因缺失小鼠BMSCs分离、培养和鉴定,初步探索DDR2基因缺失在在成骨过程中的作用结果,为进一步研究提高BMSCs的成骨分化能力奠定理论基础。经实验证明,DDR2基因缺失小鼠来源的骨髓间充质干细胞虽然仍具备干细胞的生物学特性,但其向成骨细胞的分化能力明显减弱,说明DDR2基因缺失对其骨髓间充质干细胞的成骨分化等有着重要的影响。     

SD大鼠骨髓间充质干细胞体外原代培养及鉴定

目的：探讨骨髓间充质干细胞（BMSCs）体外分离培养以及扩增的方法并鉴定。方法：取100g左右雄性SD大鼠后肢股骨、胫骨骨髓,原代全骨髓培养法,多次传代纯化,体外扩增后,观察细胞形态,并免疫组化及流式细胞仪检测cd34、cd90、cd105细胞因子,鉴定是否为BMSCs。结果：所获取的细胞呈长梭形,呈现特征性的漩涡状生长,CD34阴性,CD90、CD105阳性。结论：利用全骨髓培养法成功分离骨髓间充质干细胞,10代以内的细胞纯度高,活性好。全骨髓培养较为简便、易行。     

Isolation and characterization of mesenchymal stem cells from chicken bone marrow

The bone marrow mesenchymal stem cells (BMSCs) are multipotent stem cells, which can differentiate in vitro into many cell types. However, the vast majority of experimental materials were obtained from human, mouse, rabbit and other mammals, but rarely in poultry. So, in this study, Thirty- to sixty-day old chicken was chosen as experimental animal, to isolate and characterize BMSCs from them. To investigate the biological characteristics of chicken BMSCs, immunofluorescence and RT-PCR were used to detect the characteristic surface markers of BMSCs. Growth curves were drawn in accordance with cell numbers. To assess the differentiation capacity of the BMSCs, cells were induced to differentiate into osteoblasts, adipocytes, and endothelial cells. The surface markers of BMSCs, CD29, CD44, CD31, CD34, CD71 and CD73, were detected by immunofluorescence and RT-PCR assays. The growth curves of different passages were all typically sigmoidal. Karyotype analysis showed that these in vitro cultured cells were genetically stable. In addition, BMSCs were successfully induced to differentiate into osteoblasts, adipocytes, and endothelial cells. The results suggest that the BMSCs isolated from chicken possess similar biological characteristics with those separated from other species, and their multi-lineage differentiation potentiality herald a probable application for cellular transplant therapy in tissue engineering.     

The comparition of biological characteristics and multilineage differentiation of bone marrow and adipose derived Mesenchymal stem cells

We compared the two sources of adipose and bone marrow-derived mesenchymal stem cells (BMSCs and AMSCs ) in multiple differentiation capacity and biological characteristics to provide a theoretical basis for stem cells transplantation. We isolated bone marrow- and adipose-derived mesenchymal stem cells and compared their phenotype,cell doubling time, the secretion of factors and their ability of multi-differentiation. We also compared their differences in T lymphocyte activation, proliferation and suppression. BMSCs and AMSCs were similar in cell phenotype and the differences existed only in the expression of CD106. On the proliferation rate, AMSCs were faster than BMSCs (doubling time 28 vs. 39?h). In addition, both of these two sources of cells were able to differentiate into bone, fat and cartilage that proved their stem cells properties and the number of stem cell progenitors (CFU-F) from adipose tissue were 10 times larger than those from bone marrow. But AMSCs showed a diminished capacity for suppressing T lymphocyte proliferation and activation compared to BMSCs. Cell origin and abundance were decisive factors in stem cells applications and, in the same volume, with the same premise of AMSCs and BMSCs, adipose tissue is a more promising source of stem cells.     

氯化锂对兔骨髓间充质干细胞增殖影响

目的研究Wnt/β-catenin通路激活剂氯化锂（LiCl）对兔骨髓间充质干细胞（bone marrowmesen-chymal stem cells,BMSCs）增殖的影响。方法体外纯化培养兔BMSCs,流式细胞仪检测细胞表面抗体,以不同浓度的LiCl作用兔骨髓间充质干细胞24h后,采用Cell Counting Kit-8（CCK-8）检测各组细胞的增殖活性。结果低浓度LiCl促进兔BMSCs增殖,高浓度LiCl抑制兔BMSCs增殖。结论低浓度LiCl抑制GSK3β,模拟激活Wnt/β-catenin信号途径,从而促进细胞增殖,而高浓度LiCl增加了对细胞的毒性而抑制其增殖。     

Differentiation of Rabbit Bone Mesenchymal Stem Cells into Endothelial Cells In Vitro and Promotion of Defective Bone Regeneration In Vivo

Tissue engineering strategies often fail to regenerate bones because of inadequate vascularization, especially in the reconstruction of large segmental bone defects. Large volumes of vascular endothelial cells (ECs) that functionally interact with osteoblasts during osteogenesis are difficult to obtain. In this study, we simulated bone healing by co-culturing differentiated ECs and mesenchymal stem cells (MSCs) either on a culture plate or on a polylactide glycolic acid (PLGA) scaffold in vitro. We also evaluated the effect of osteogenesis in repairing rabbit mandible defects in vivo. In this study, MSCs were separated from rabbit as the seed cells. After passage, the MSCs were cultured in an EC-conditioned medium to differentiate into ECs. Immunohistochemical staining analysis with CD34 showed that the induced cells had the characteristics of ECs and MSC. The induced ECs were co-cultured in vitro, and the induction of MSCs to osteoblast served as the control. Alkaline phosphatase (ALP) and alizarin red (AZR) staining experiments were performed, and the Coomassie brilliant blue total protein and ALP activity were measured. The MSCs proliferated and differentiated into osteoblast-like cells through direct contact between the derived ECs and MSCs. The co-cultured cells were seeded on PLGA scaffold to repair 1 cm mandible defects in the rabbit. The effectiveness of the repairs was assessed through soft X-ray and histological analyses. The main findings indicated that MSCs survived well on the scaffold and that the scaffold is biocompatible and noncytotoxic. The results demonstrated that the co-cultured MSC-derived ECs improved MSC osteogenesis and promoted new bone formation. This study may serve as a basis for the use of in vitro co-culturing techniques as an improvisation to bone tissue engineering for the repair of large bone defects.     

兔骨髓间充质干细胞的分离、培养与鉴定

目的:寻求家兔骨髓间充质干细胞(Bone Mesenchymal Stem cells,BMSCs)培养与分离简单易行的方法,为下一步骨髓间充质干细胞在呼吸系统疾病的应用打好基础。方法:取3个月龄家兔1只,经双侧髂前上棘抽取骨髓共5.0 ml,密度梯度离心法和贴壁筛选法相结合分离、纯化获得BMSCs,倒置差显微镜观察其形态学特性,流式细胞仪鉴定CD34、CD133表达。结果:接种细胞于24小时有少量细胞贴壁,72小时多数细胞可贴壁,贴壁细胞形态多为长梭型或多边形,原代细胞呈集落生长,12-16天可达90%融合,1%胰酶消化后传代培养,培养至第三代备用。流式细胞仪鉴定90%为骨髓间充质干细胞。结论:通过密度梯度离心法与贴壁筛选法可成功分离培养出骨髓间充质干细胞,此方法简单易行,成功率比较高。     

SD大鼠骨髓间充质干细胞体外原代培养及鉴定

目的:探讨骨髓间充质干细胞(BMSCs)体外分离培养以及扩增的方法并鉴定。方法:取100g左右雄性SD大鼠后肢股骨、胫骨骨髓,原代全骨髓培养法,多次传代纯化,体外扩增后,观察细胞形态,并免疫组化及流式细胞仪检测cd34、cd90、cd105细胞因子,鉴定是否为BMSCs。结果:所获取的细胞呈长梭形,呈现特征性的漩涡状生长,CD34阴性,CD90、CD105阳性。结论:利用全骨髓培养法成功分离骨髓间充质干细胞,10代以内的细胞纯度高,活性好。全骨髓培养较为简便、易行。     

Stromal stem cells from adipose tissue and bone marrow of age‐matched female donors display distinct immunophenotypic profiles

Adipose tissue is composed of lipid‐filled mature adipocytes and a heterogeneous stromal vascular fraction (SVF) population of cells. Similarly, the bone marrow (BM) is composed of multiple cell types including adipocytes, hematopoietic, osteoprogenitor, and stromal cells necessary to support hematopoiesis. Both adipose and BM contain a population of mesenchymal stromal/stem cells with the potential to differentiate into multiple lineages, including adipogenic, chondrogenic, and osteogenic cells, depending on the culture conditions. In this study we have shown that human adipose‐derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) populations display a common expression profile for many surface antigens, including CD29, CD49c, CD147, CD166, and HLA‐abc. Nevertheless, significant differences were noted in the expression of CD34 and its related protein, PODXL, CD36, CD 49f, CD106, and CD146. Furthermore, ASCs displayed more pronounced adipogenic differentiation capability relative to BMSC based on Oil Red staining (7‐fold vs. 2.85‐fold induction). In contrast, no difference between the stem cell types was detected for osteogenic differentiation based on Alizarin Red staining. Analysis by RT‐PCR demonstrated that both the ASC and BMSC differentiated adipocytes and osteoblast displayed a significant upregulation of lineage‐specific mRNAs relative to the undifferentiated cell populations; no significant differences in fold mRNA induction was noted between ASCs and BMSCs. In conclusion, these results demonstrate human ASCs and BMSCs display distinct immunophenotypes based on surface positivity and expression intensity as well as differences in adipogenic differentiation. The findings support the use of both human ASCs and BMSCs for clinical regenerative medicine. J. Cell. Physiol. 226: 843–851, 2011. © 2010 Wiley‐Liss, Inc.     

Bone marrow mesenchymal stem cells differentiate into urothelial cells and the implications for reconstructing urinary bladder mucosa

To determine the ability of cultured bone marrow-derived mesenchymal stem cells (BMSCs) to differentiate into functional urothelium. BMSCs were isolated from the long bones of aborted fetal limbs by Percoll density gradient centrifugation and characterized by flow cytometry. Human fetal urinary bladders were cut into small pieces and cultured for 3–5 days until the growth of urothelial cells was established. BMSCs were then cocultured with neonatal urothelial cells and subsequently evaluated for antigen expression and ultramicrostructure, by immunocytochemistry and electron microscopy, respectively. A subset of BMSCs expressed the differentiation marker CD71. The BMSC markers CD34, CD45, and HLA-DR were barely detectable, confirming that these cells were not derived from hematopoietic stem cells or differentiated cells. In contrast, the stem cell markers CD29, CD44, CD105, and CD90 were highly expressed. BMSCs possessed the ability to differentiate into a variety of cellular subtypes, including osteocytes, adipocytes, and chondrocytes. The shapes of BMSCs changed, and the size of the cells increased, following in vitro coculture with urothelial cells. After 2 weeks of coculture, immunostaining of the newly differentiated BMSCs positively displayed the urothelial-specific keratin marker. Electron microscopy revealed that the cocultured BMSCs had microstructural features characteristic of epithelial cells. Pluripotent BMSCs can transdifferentiate into urothelial cells in response to an environment conditioned by neonatal urothelial cells, providing a means for the time-, labor- and cost-effective reconstruction of urinary bladder mucosa.     

Comparison of gingiva‐derived and bone marrow mesenchymal stem cells for osteogenesis

Presently, bone marrow is considered as a prime source of mesenchymal stem cells; however, there are some drawbacks and limitations. Compared with other mesenchymal stem cell (MSC) sources, gingiva‐derived mesenchymal stem cells (GMSCs) are abundant and easy to obtain through minimally invasive cell isolation techniques. In this study, MSCs derived from gingiva and bone marrow were isolated and cultured from mice. GMSCs were characterized by osteogenic, adipogenic and chondrogenic differentiation, and flow cytometry. Compared with bone marrow MSCs (BMSCs), the proliferation capacity was judged by CCK‐8 proliferation assay. Osteogenic differentiation was assessed by ALP staining, ALP assay and Alizarin red staining. RT‐qPCR was performed for ALP, OCN, OSX and Runx2. The results indicated that GMSCs showed higher proliferative capacity than BMSCs. GMSCs turned more positive for ALP and formed a more number of mineralized nodules than BMSCs after osteogenic induction. RT‐qPCR revealed that the expression of ALP, OCN, OSX and Runx2 was significantly increased in the GMSCs compared with that in BMSCs. Moreover, it was found that the number of CD90‐positive cells in GMSCs elevated more than that of BMSCs during osteogenic induction. Taking these results together, it was indicated that GMSCs might be a promising source in the future bone tissue engineering.     

Enhancement of bone formation by genetically-engineered bone marrow stromal cells expressing BMP-2, VEGF and angiopoietin-1

To explore the potential of combined delivery of osteogenic and angiogenic factors to bone marrow stromal cells (BMSCs) for repair of critical-size bone defects, we followed the formation of bone and vessels in tissue-engineered constructs in nude mice and rabbit bone defects upon introducing different combinations of BMP-2, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) to BMSCs with adenoviral vectors. Better osteogenesis and angiogenesis were found in co-delivery group of BMP-2, VEGF and angiopoietin-1 than any other combination of these factors in both animal models, indicating combined gene delivery of angiopoietin-1 and VEGF165 into a tissue-engineered construct produces an additive effect on BMP-2-induced osteogenesis.     

表面改性双相陶瓷复合自体骨髓干细胞修复兔骨缺损的实验研究

目的:应用自体骨髓基质干细胞(Bone Marrow Stromal Cells,BMSCs)复合经低晶态羟基磷灰石(Low Crystalline Hydroxyap- atite,LcHA)涂层的双相陶瓷(Biphasic Calcium Phosphate,BCP)构建的组织工程化骨(LcBCP)修复兔桡骨节段性缺损。方法:体外分离培养、诱导扩增兔BMSCs,取第三代细胞复合LcBCP(实验组)后修复15只兔左侧桡骨15mm缺损;右侧桡骨缺损处植入复合BMSCs的BCP(对照组),于植入后4、8和12周处死动物,通过大体形态、组织学、影像学和扫描电镜检测骨缺损修复效果。结果:BMSCs-LcBCP复合物生长良好,随时间延长,X线显示实验组连接处骨痂形成,对照组连接处始终愈合稍差,12周大体观察实验组骨修复良好,髓腔再通;组织学显示板层骨形成,连接处骨性愈合,实验对照组连接处虽然也为骨性愈合,但尚有较多编织骨形成。结论:自体BMSCs复合LcBCP形成的组织工程化骨可修复兔桡骨节段性缺损,低晶态羟基磷灰石涂层能够增强双相陶瓷的早期成骨。     

M-CSF诱导人骨髓间充质干细胞分化为肝样细胞的分子机制

本研究主要目的是明确M-CSF诱导骨髓间充质干细胞分化为肝样细胞的分子机制,为临床中的肝移植和治疗肝病提供新思路。对取自于本院骨科治疗的患者的股骨骨髓间充质干细胞进行提取、分离、传代培养及鉴定。流式细胞仪检测BMSCs的表面表型。为了诱导BMSCs的肝分化,本研究将BMSCs加入到培养基中。骨髓间充质干细胞诱导21 d后,BMSCs表达了肝细胞特异性标志物a-蛋白(AFP)和细胞角蛋白18(CK18),通过免疫荧光染色证实了分化与为分化的BMSCs表达的差异性。分化的BMSCs还显示了肝细胞的体外功能特征,包括白蛋白产生、尿素分泌和糖原储存。本研究结果表明,BMSCs在M-CSF诱导下可分化为功能性肝细胞样细胞,可作为肝病治疗的细胞来源。     

Dimethyloxaloylglycine Improves Angiogenic Activity of Bone Marrow Stromal Cells in the Tissue-Engineered Bone

One of the big challenges in tissue engineering for treating large bone defects is to promote the angiogenesis of the tissue-engineered bone. Hypoxia inducible factor-1α (HIF-1α) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, and can activate a broad array of angiogenic factors. Dimethyloxaloylglycine (DMOG) can activate HIF-1α expression in cells at normal oxygen tension. In this study, we explored the effect of DMOG on the angiogenic activity of bone mesenchymal stem cells (BMSCs) in the tissue-engineered bone. The effect of different concentrations of DMOG on HIF-1a expression in BMSCs was detected with western blotting, and the mRNA expression and secretion of related angiogenic factors in DMOG-treated BMSCs were respectively analyzed using qRT-PCR and enzyme linked immunosorbent assay. The tissue-engineered bone constructed with β-tricalcium phosphate (β-TCP) and DMOG-treated BMSCs were implanted into the critical-sized calvarial defects to test the effectiveness of DMOG in improving the angiogenic activity of BMSCs in the tissue-engineered bone. The results showed DMOG significantly enhanced the mRNA expression and secretion of related angiogenic factors in BMSCs by activating the expression of HIF-1α. More newly formed blood vessels were observed in the group treated with β-TCP and DMOG-treated BMSCs than in other groups. And there were also more bone regeneration in the group treated with β-TCP and DMOG-treated BMSCs. Therefore, we believed DMOG could enhance the angiogenic activity of BMSCs by activating the expression of HIF-1α, thereby improve the angiogenesis of the tissue-engineered bone and its bone healing capacity.     

IGF-1 and BMP-7 synergistically stimulate articular cartilage repairing in the rabbit knees by improving chondrogenic differentiation of bone-marrow mesenchymal stem cells

Knee injury is known as a frequently occurred damage related to sports, which may affect the function of cartilage. This study aims to explore whether Insulin-like growth factor 1 (IGF-1) and bone morphogenetic protein-7 (BMP-7)-modified bone-marrow mesenchymal stem cells (BMSCs) affect the repair of cartilage damage found in the knee. Primarily, BMSCs were treated with a series of pEGFP-C1, IGF-1, and BMP-7, followed by determination of IGF-1 and BMP-7 expression. A rabbit cartilage defect model was also established. Afterfward, cell morphology, viability, cartilage damage repair effect, and expression of collagen I and collagen II at the 6th and the 12th week were measured. BMSCs treated with pEGFP-C1/IGF-1, pEGFP-C1/BMP-7, and pEGFP-C1/BMP-7-IGF-1 exhibited elevated expression of BMP-7 and IGF-1. Besides, BMSCs in the P10 generation displayed decreased cell proliferation. Moreover, BMSCs treated with IGF-1, BMP-7, and IGF-1-BMP-7 showed reduced histological score and collagen I expression while elevated collagen II expression, as well as better repair effect, especially in those treated with IGF-1-BMP-7. Collectively, these results demonstrated a synergistic effect of IGF-1 and BMP-7 on the BMSC chondrogenic differentiation on the articular cartilage damage repair in the rabbit knees, highlighting its therapeutic potential for the treatment of articular cartilage damage.