骨髓间充质干细胞移植联合髓芯减压植骨修复股骨头坏死

doi:10.3969/j.issn.2095-4344.2015.06.011

摘要/Abstract

摘要：

背景：单独使用髓芯减压治疗股骨头坏死，易造成股骨头凹陷和内部显微结构的崩溃，因而需要自体骨等材料进行填充支撑，而骨髓干细胞移植能使股骨头塌陷的发生率降低。
目的：观察髓芯减压植骨联合骨髓间充质干细胞移植治疗股骨头坏死的临床效果。
方法：选择2012年12月至2013年5月在沈阳医学院附属中心医院骨外四科住院的33例采用股骨头髓芯减压植骨联合骨髓间充质干细胞注入髓腔内治疗股骨头坏死患者。
结果与结论：股骨头髓芯减压植骨联合骨髓间充质干细胞注入髓腔内治疗股骨头坏死后患者Harris髋关节功能评分增加，疼痛消失，能从事各种劳动；X射线片或CT检查显示股骨头正常30髋，占79%；疼痛明显减轻，行走基本正常或者轻微跛行15髋，占40%；行走间距延长35髋，占92%；髋关节功能障碍明显好转24髋，占63%。提示髓芯减压植骨联合骨髓间充质干细胞移植对改善股骨头缺血性坏死局部血供，促进坏死骨质吸收和骨质修复起到积极的作用。

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

关键词: 干细胞, 移植, 股骨头坏死, 髓芯减压, 植骨, 骨髓间充质干细胞, Ficat分期

Abstract:

BACKGROUND: Core decompression alone for osteonecrosis of femoral head easily causes fovea of femoral head and collapse of inner microstructure. Therefore, autologous bone is needed for filling and supporting. Moreover, bone marrow stem cell transplantation can decrease the incidence of femoral head collapse.
OBJECTIVE: To discuss the clinical effects of core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells for osteonecrosis of femoral head.
METHODS: A total of 33 patients were treated by core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells in the Fourth Department of Bone Surgery, Central Hospital Affiliated to Shenyang Medical College in China from December 2012 to May 2013.
RESULTS AND CONCLUSION: After the treatment by core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells, Harris hip function score increased and pain disappeared in patients with osteonecrosis of femoral head. They could do various labors. Radiographs or CT examination displayed normal femoral head in 30 hips, accounting for 79%. Pain significantly reduced. Normal or slight limp walking was found in 15 hips, accounting for 40%. There were 35 hips in patients, whose walking distance was extended, accounting for 92%. 24 hips dysfunction was improved markedly, accounting for 63%. All results suggested that core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells improved the local blood supply of femoral head, and played a positive role in promoting the necrotic bone absorption and bone repairing.

全文链接：

Key words: Femur Head Necrosis, Decompression, Mesenchymal Stem Cell Transplantation, Femur Head

中图分类号:

R394.2

张洋，王楠，杨立枫，马骥，李治. 骨髓间充质干细胞移植联合髓芯减压植骨修复股骨头坏死[J]. 中国组织工程研究, 2015, 19(6): 883-890.

Zhang Yang, Wang Nan, Yang Li-feng, Ma Ji, Li Zhi. Bone marrow mesenchymal stem cell transplantation combined with core decompression and bone grafting in the repair of osteonecrosis of femoral head[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(6): 883-890.

图/表（结果） 4

Isolation and culture of human BMSCs

Human BMSCs were successfully isolated and cultured. Cell morphology is displayed in Figure 1.

Analysis of the number of patients and clinical information

All patients were involved in the final analysis. Patients and clinical information are listed in Table 1.

Hip function score in patients with osteonecrosis of femoral head

Patients received core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells. A total of 33 patients were followed up at 6-12 months after implantation. Radiographs or CT images did not reveal further collapse of the femoral head. The region of necrosis of the femoral head was controlled and noticeably improved. According to Harris hip function score, pain disappeared and they could do various works. X-ray and CT detection demonstrated that 30 hips had normal femoral head, accounting for 79%; pain apparently lessened; normal walking or slightly limping was detected in 15 hips, accounting for 40%. Walking distance extended in 35 hips, accounting for 92%. Hip dysfunction evidently improved in 24 hips, accounting for 63%. Harris score in patients with osteonecrosis of femoral head before and after implantation is shown in Table 2.

Typical cases

Case 1: a 34-year-old male patient suffered from necrosis of

left femoral head, and underwent core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells (Figures 2A-C). Pain in the left hip obviously relieved at 1 week after transplantation, and basically lessened at 3 months.

Case 2: a 35-year-old male patient experienced right necrosis of the femoral head, and received core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells (Figures 2D-F). Pain lessened somewhat after implantation, relieved basically at 3 months, and basically disappeared at 12 months. The activity was normal.

Adverse reactions

One patient suffered from high blood pressure. One patient had joint effusion with a safety factor of 94%. Their bodies recovered to normal after corresponding treatment. Symptoms disappeared after taking corresponding measures.

参考文献

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引言

Osteonecrosis of femoral head is a common disease in the department of orthopedics. Various reasons induce the interrupted or impaired blood supply within the femoral head, cell death in the femoral head, changes in the structure of the femoral head, and joint dysfunction^[1]. The main reason for osteonecrosis of femoral head contains heavy drinking, the long-term use of hormones, trauma, vascular malformations, and connective tissue diseases^[2]. A previous study demonstrated that osteonecrosis of femoral head in China mainly appears in young people, and often involves multiple joints, seriously impacted quality of life in patients^[3]. Moreover, osteonecrosis of femoral head severely damages the hip joint, and the prognosis is not ideal^[4-5]. Therefore, how to perform active effective therapy in early onset of osteonecrosis of femoral head, and to find the method to retain autologous femoral head to avoid or delay arthroplasty is the key in present researches.

Core decompression by drilling is a mature method to treat early osteonecrosis of femoral head and the main method to treat early osteonecrosis of femoral head. The aim is to reduce the pressure within the femoral head. Moreover, to stimulate the formation of capillary vessels surrounding the nail hole and to enhance creeping substitution of bone necrosis are helpful to the repair and improvement of necrotic bone^[6]. However, the removal of necrotic tissue in the bone by core decompression can cause the loss of complete mechanical support of already weak subchondral bone, easily lead to fovea of femoral head and collapse of inner.

Microstructure. At present, various materials including autologous bone are used as support for filling after core decompression^[7], but the therapeutic effects are poor. Currently, stem cells for treating avascular necrosis of the femoral head are a hot focus. Basic experimental researches have verified that stem cells can differentiate into osteoblasts under specific conditions, which are important factors during the repair of bone necrosis. In addition, a previous study suggested that concentrated bone marrow stem cells transplanted into the necrotic femoral head could decrease the incidence of collapse of the femoral head^[8]. Bone marrow of adults consists of two kinds of cells, i.e., bone marrow hemopoietic stem cells and bone marrow mesenchymal stem cells (BMSCs). BMSCs are derived from the early developed mesoderm and ectoderm, a class of cells with multiple differentiation potentials, can differentiate into osteoblasts, chondrocytes, adipocytes, myoblasts, neurons and glial cells under certain conditions^[9-10], as well as other tissues derived from mesenchymal cells. Moreover, BMSCs can be easily collected, isolated, cultured, have strong immunogenicity, weak proliferative capacity in vitro, keep the potential of multi-directional differentiation during subculture, which makes BMSCs become ideal seed cells for repair of bone necrosis^[11]. To find early and give a safe effective therapy, this study used core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells for treating avascular necrosis of the femoral head, obtained apparent therapeutic effects. Reports on 33 patients with complete follow-up data and 33 hips are as follows:

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程
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材料方法

SUBJECTS AND METHODS

Design

A clinical study.

Time and setting

Experiments were performed in the Fourth Department of Bone Surgery, Central Hospital Affiliated to Shenyang Medical College in China from December 2012 to May 2013.

Subjects

Patients with osteonecrosis of femoral head, who were treated in the Fourth Department of Bone Surgery, Central Hospital Affiliated to Shenyang Medical College in China from December 2012 to May 2013, were enrolled in this study.

Diagnostic criteria

All subjects were in accordance with Common Understanding of Diagnosis and Treatment for Necrotic Femoral Heads in Adults in 2012^[12]. (1) Clinical symptoms, signs and medical history of joint pain on groin, buttocks and thighs, sometimes accompanying knee joint pain, restricted rotation activities within the hip; often hip injury history, the history of corticosteroid use, alcohol abuse, and divers. (2) T1WI of MRI revealed that ribbon low signal or T2WI revealed double lines. (3) Radiographs showed sclerosis, cystic and crescent sign. (4) CT scanning altered necrotic bone surrounding sclerosis, repaired bone or subchondral bone fracture. (5) Early radionuclide bone scan showed perfusion defects (cold zone); during repair, “donut-like” changes were visible in the hot zone. (6) Bone biopsy demonstrated that empty lacunae of trabecular bone cells was more than 50%, involved in many adjacent trabeculae, and necrosis of bone marrow. Patients accorded with two or more criteria were diagnosed. Except (1), patients according with one criterion of (2), (3), (4) and (6) were diagnosed.

Inclusion criteria

(1) Diagnostic criteria; (2) Belong to stages I and II of Ficat of necrosis of the femoral head; (3) no related surgery or drug contraindications; (4) agree to autotransplantation of BMSCs, and signed informed consent.

Exclusion criteria

(1) Do not accord with the diagnostic criteria of necrosis of the femoral head; (2) collapse of the femoral head in stages III and IV of Ficat; (3) pregnant or lactating women; (4) combined with severe primary diseases such as organ disease, cancer and endocrine systems and mental illness; (5) need to continue long-term use of hormone therapy; (6) less than 18 years old or more than 60 years old.

Staging criteria

Ficat staging contains stages 0-IV. Stage 0: pre-clinic, no clinical symptom, no abnormal changes in imaging; stage I: pain, normal radiographs, abnormal bone scanning and MRI detection; stage II: IIa, pain, obvious symptom, X-ray plain films showed extensive osteoporosis, scattered sclerosis or cystic bone, but the shape of the femoral head is normal, no collapse; IIb, X-ray plain films revealed trabecular changes, local sclerosis or formation of upward arc sclerosis; thinning area is visible in subchondral bone; top of the femoral head collapses within 2 mm; normal joint space; abnormal bone scanning and MRI detection, but no subchondral fracture. Stage III: clinical symptoms get worse; X-ray plain films reveal that besides cystic changes in hardening zone within the femoral head, the femoral head collapses > 2 mm, with the presence of crescent sign. Bone scan and MRI detection showed subchondral collapse and (or) step-like collapse of subchondral bone, and normal joint space. Stage IV: stage of osteoarthritis, noticeable hip pain; range of motion of hip joint obviously shortens; X-ray plain films demonstrate collapse in the top of the femoral head, and narrow joint space^[13].

A total of 33 patients with osteonecrosis of femoral head, including 25 males and 8 females, at the age of 33-58 years old, averagely 44.2 years, were included. Cause of the disease: long-term drinking in 15 cases, post-trauma in 14 cases, long-term use of hormone in 3 cases, and unexplained in 1 case. Patients underwent X-ray, CT and MRI detection before implantation. The lesion is involved in left hip joint in 13 cases, right hip joint in 15 cases, and bilateral hip joint in 5 cases, totally 38 joints. According to Ficat staging, there were 17 hips of stage I and 21 hips of stage II. Sample collection was approved by the Ethics Committee of Central Hospital Affiliated to Shenyang Medical College in China, and patients signed informed consent. The protocols were conducted in accordance with the medical ethics standards.

Methods

Collection of bone marrow

Samples were collected at 2 weeks before transplantation. Puncture was done at anterior superior iliac spine with a No. 16 bone needle. 6 mL bone marrow blood was obtained with heparin-treated syringe. After shaking and mixing, blood was equally stored in two 15 mL sterile centrifuge tubes, each containing 3 mL. Human bone marrow stem cell isolation and purification kit (Zhonglian Dasheng Biotechnology Company) was used for isolation to obtain cell suspension for cell counting. Cells at the concentration of 5×10⁵/cm² were seeded in cell culture flask, and then placed in an incubator at 37 °C and 5% CO₂ for 72 hours. The medium was first replaced. Suspended cells were discarded. From then on, the medium was replaced every 2 days. Under the inverted microscope, cells grew well and were subcultured at 80% confluence. The medium was discarded. Samples were washed three times with PBS, treated with 0.25% trypsin 1 mL, and observed under a microscope (Olympus, Japan). When cell processes disappeared and cells became round, digestive juice was discarded immediately. The digestion was terminated with the medium. Adherent cells were triturated with a pipette into single-cell suspensions. According to appreciable proportion, cells were subcultured in different tubes, and cultured in the incubator. The medium was replaced every other day for further incubation.

Therapeutic methods

In accordance with CT and MRI results before transplantation, the necrotic foci were repeatedly identified. C-arm X-ray fluoroscopy showed lateral femoral shaft. Drilling direction, position and depth were designed in advance. A Kirschner wire of 3 mm diameter as a guide pin was drilled below the lateral greater trochanter of affected hip, traversed the center from neck of femur to the necrotic region of the femoral head, mainly located in the anterior superior region of the femoral head. The needle tip reached 5 mm below the articular surface. A

2 cm longitudinal incision was made along the guide pin. A hole was drilled with a trephine of 10 mm diameter along the guide pin. Cancellous bone from greater trochanter and femoral neck was obtained for bone graft, washed, and dried with gauze. Third passage BMSC (2×10⁷) suspension 2-3 mL was infused into the cancellous bone for further use. Hollow drill of 10 mm diameter was used to drill into the necrotic region of the femoral head along the guide pin. Necrotic tissue was completely removed with a long-handled spoon-shaped elbow curette at different angles. When the trephine traversed the necrotic region, the resistance was apparently increased. At this time, it should be noted to slowly drill by gradually force and avoid excessive force injuring cartilage. The bone tunnel was washed cleanly. The cancellous bone with bone marrow blood was implanted in the necrotic region along the bone tunnel, which was blocked with bone wax so as to reduce the outleakage of cells. If the wound did not have active bleeding, the incision was sutured layer by layer.

Postoperative management

After implantation, patients did not try to use or less use antibiotic. After resting on the bed, patients could ambulate. Within 6 months, the affected limbs could not bear, but could bear after 6 months according to the follow-up results. All patients were regularly followed up, received X-ray plain films or CT examination and relevant knowledge education. At 12 months after transplantation, patients could move freely.

Gross observation

Patients were followed up at 3, 6, 9 and 12 months after core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells. We observed hip pain, the nature of pain and pain time, travel distance and gait, hip abduction and internal rotation function.

Evaluation for hip joint function

Harris score was used to observe the degree of hip pain and assess the hip function^[14]. Harris score contained pain, function, malformation and range of motion.

Imaging observation

X-ray and CT were utilized to observe the changes in bone in the femoral head, the progression of the necrotic femoral head, and the whether the collapse appearance.

Main outcome measures

Therapeutic outcomes of core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cells.

Statistical analysis

Data were analyzed using SPSS 18.0 software and expressed as mean ± SD. Paired t-test was used. Harris hip joint function score was statistically analyzed before transplantation and during final follow-up. A value of P < 0.05 was considered statistically significant.

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讨论

The treatment for osteonecrosis of femoral head is a difficulty in the department of orthopedics. Its onset can be mainly found in young people. Moreover, the incidence shows an increased trend year by year. Inopportune treatment in early stage will induce progressive bone destruction and increase bone resorption. The reduction in support structure under the joint will cause collapse of the articular surface of the femoral head and osteoarthritis, and severely affect quality of life. Therefore, to find a safe and effective therapeutic method is a hot focus in the research of department of orthopedics^[15]. Core decompression can effectively reduce the increased intraosseous pressure in the affected femoral head. Therefore, core decompression has a certain therapeutic effect in early treatment of osteonecrosis of femoral head.

This method is occasionally found by Ficat when he used hollow circular saw to make femoral marrow core biopsy^[16], so this technique is called core decompression. From then on, this finding has been extensively utilized in treatment of avascular necrosis of the femoral head. Core decompression has been verified to stimulate the formation of blood vessels surrounding the needle hole, to enhance creeping substitution of necrotic bone^[17-18]. After intra-articular pressure of the hip joint was relieved, fresh wound was formed, which was helpful to the establishment of collateral circulation^[19]. However, this repair is only limited in local region. Due to insufficient creeping substitution and bone remodeling, it is not complete to reconstruct the necrotic region using core decompression, and its clinical outcomes are not satisfactory^[20]. Latest studies suggested that stem cells have the potential of multi-directional differentiation, can differentiate into other cells under certain conditions so as to promote the repair of injured tissue. BMSCs are fiber colony-forming cells and have been known since 1970s^[21]. BMSCs can differentiate into osteoblasts, chondrocytes and epithelial cells, are easily obtained and isolated, have weak immunogenicity^[22]. Thus, BMSCs have been acclaimed in the study of necrosis of the femoral head. A previous study demonstrated that transplanted BMSCs in the necrotic region of the femoral head could survive, proliferate and differentiate into various cells, involve in the bone repair, bone formation and angiogenesis^[23]. Recently, the combined application of core decompression and bone marrow stem cell transplantation has been widely used for treatment of avascular necrosis of the femoral head^[24-26].

Many previous studies compared the therapeutic effects of core decompression combined with BMSC transplantation with core decompression alone, and demonstrated that the outcomes of their combination were significantly better than core decompression alone^[27]. Core decompression is most commonly used in patients without collapse of the femoral head in the stages I and II, and also effective for cases of collapse of the femoral head in the stage III, but the outcomes are not ideal^[27]. Taken together, this study selected 33 cases of osteonecrosis of femoral head in stages of I and II. In this study, on the basis of core decompression, autologous cancellous bone carrying BMSCs was implanted, which could improve intraosseous pressure and bone microcirculation, provide seed cells for femoral reconstruction and good environment for new bone formation. After implantation, patients were followed up at 12 months. Most patients could walk with loading after implantation, and pain symptoms lessened. Imaging results revealed that the volume of necrotic region of the femoral head obviously reduced. Hip evaluation criteria showed that score increased and reached good standard. Hernigou et al ^[28] performed core decompression combined with autologous bone marrow transplantation for treatment of necrosis of the femoral head in 116 cases of 189 hips, who were followed up for 5-10 years. Hernigou et al ^[28] believed that BMSC transplantation had good effects on early necrosis of the femoral head. Chu et al ^[29] used the same method to treat ischemic femoral head necrosis in the elderly, and results showed that patients did not experience uneven density and cystic changes after core decompression and cancellous bone implantation combined with autologous bone marrow stem cell transplantation. Moreover, necrotic bone was mostly replaced by new bone. Only two patients suffered from deterioration of disease, which progressed to phase III 16 months later. Among patients only undergoing core decompression and cancellous bone implantation, four patients (five hips) experienced uneven density and cystic alterations at 6 months after implantation, and progressed to phase III. Above results confirmed that core decompression combined with BMSC transplantation had significant therapeutic outcomes on patients with early necrosis of the femoral head.

The mechanism of BMSCs for necrosis of the femoral head is possibly as follows: (1) BMSCs with the capability of multi-directional differentiation can differentiate into osteoblasts and chondrocytes under certain conditions, enhance bone formation and repair the damaged bone trabecula^[30]. A previous study confirmed that compared with embryonic stem cells, bone nodules formed by BMSCs are more closely to native bone nodules in aspects of toughness and structure^[31]. (2) BMSCs have secretion effect, stimulate vascular wall to secrete growth factors, simulate extracellular matrix of in vivo microenvironment, induce growth factors growing towards the area of necrosis, and promote the healing of necrotic region of the femoral head^[32]. (3) BMSCs contribute to the repair, regeneration and angiogenesis of vascular endothelial cells, promote the formation of collateral circulation, rebuild blood circulation system, improve blood supply in the necrotic region, and eliminate the etiological factor for ischemic necrosis of the femoral head^[33]. (4) Autologous BMSCs also reduce the risk of immune rejection^[34]. Above characteristics determine that BMSCs can be used as ideal seed cells for repair of bone and joint. Therefore, the number of BMSC collection and the time and pathway of stem cell transplantation are main factors for the therapeutic effects of stem cell transplantation. During transplantation, abundant BMSCs are needed. The extraction of a large number of bone marrow blood is a heavy burden for patient’s health. BMSCs have the potential of self-renewal. After passage, BMSCs can keep biological properties. A previous study demonstrated that BMSCs at passage 38 can still maintain the directed differentiation potential. Karyotype and telomerase activity do not alter with multi-generational culture^[35]. Therefore, this study performed in vitro amplification using autologous BMSCs, and obtained a large number of seed cells, simultaneously maintained proliferative capacity and characteristics of BMSCs, and reduced patient’s healthy burden.

The precise advantages of core decompression and bone grafting combined with BMSC transplantation are as follows: (1) core decompression and bone grafting combined with BMSC transplantation can delay the necrosis of the femoral head, reach healing or prevent, delay the progression of pathogenetic condition, finally avoid or delay the time of arthroplasty^[36], and do not impact future joint replacement. (2) Full core decompression lessens the high pressure in the femoral head, improves local blood transport, and is helpful to the bone formation and vascular generation. Simultaneously, lesion cleanup and implantation of autologous cancellous bone with BMSCs are conducted. The implantation of cancellous bone plays a role as carrier. BMSCs can directly enter fresh cancellous bone, which contributes to stem cell diffusion and prevents collapse. (3) Minimal invasion, rapid operation time, rapid postoperative restoration, safe, effective, simple, convenient, nearly no complications, no ethical issues and rejection issues. The outcomes of therapeutic alliance are evident, but some details should be further defined. A study demonstrated that core decompression and bone marrow stem cell transplantation obtained good outcomes of early necrosis of the femoral head (stages I and II)^[27], but the outcomes for large lesion range of stages III and IV are not ideal^[37]. Simultaneously, bone grafting is commonly used in young patients at Ficat II - III stages, because a large part of the articular surface of the femoral head of these patients is not damaged. After removal of necrotic tissue, adequate bone grafting could effectively prevent the collapse of the femoral head^[38]. Therefore, core decompression combined with BMSC transplantation provides a thinking for treatment of ischemic necrosis of the femoral head in Ficat III stage. Replacement therapy can also be used for patients with weak physical condition and who are not suitable for patients undergoing total hip replacement.

In summary, core decompression combined with BMSC transplantation plays active role in ameliorating local blood supply of avascular necrosis of the femoral head, promoting absorption of necrotic bone and the repair of bone. Patients did not experience severe complications and adverse reactions during treatment. Its safety and effectiveness have been confirmed basically, but uncorrected operation manner possibly leads to the failure of treatment. Tunnel for decompression is not in the necrotic area, does not remove the focus, but destroys normal bone. Therefore, lateral fluoroscopy should be conducted many times during guide pin is drilled. It is necessary to confirm that the guided needle reaches the middle of the necrotic area. During decompression, the drill breaks subchondral bone and injures articular surface. Excessive removal of focus will destroy the structure of the femoral head and reduce the weight-bearing capability. Sclerotic bone has support effects on the femoral head. During surgery, only necrotic bone and granulation tissue in cystic degeneration are scraped. During bone grafting, violent hammering is needed so as to cause subchondral bone microfracture^[39]. The hole was sealed with bone wax to prevent BMSC loss. Thus, many problems are needed to be solved. For example, the optimal time of stem cell transplantation and the diameter of core decompression for cell infusion deserve further investigations. The concentration and dose of autologous BMSCs should be determined. At present, there is not a method suitable for all kinds of necrosis of the femoral head. Different therapeutic methods are needed according to the type of necrosis, age and economic status. Although many problems are needed to be solved, with deepening and expansion of research, core decompression and bone grafting combined with BMSC transplantation will be really applied into the clinic, becomes a new manner to treat necrosis of the femoral head, and brings gospel for the treatment of necrosis of the femoral head.