Assessment of results of knee cartilage restoration in mri of autologous adipose stem cell therapy on treatment of knee osteoarthritis

Nội dung text: Assessment of results of knee cartilage restoration in mri of autologous adipose stem cell therapy on treatment of knee osteoarthritis

1. Journal of military parmaco-medicine n 07-2017 ASSESSMENT OF RESULTS OF KNEE CARTILAGE RESTORATION IN MRI OF AUTOLOGOUS ADIPOSE STEM CELL THERAPY ON TREATMENT OF KNEE OSTEOARTHRITIS Ta Viet Hung*; Nguyen Minh Nui*; Tran Ngoc Dung* Nguyen Thi Phi Nga*; Le Van Dong** Do Minh Trung**; Tran Viet Tien* SUMMARY Objectives: To assess results of knee cartilage restoration on MRI of autologous adipose stem cell therapy in treatment of knee osteoarthritis (OA) after 12 months. Subjects and methods: 84 patients with primary knee OA were divided into 2 groups: 42 patients were treated by autologous adipose stem cell (AASC), 42 patients were treated with sodium hyaluronate. A descriptive cross-sectional, randomized controlled study was created to evaluate the cartilage restoration on MRI of AASC group compared with control group. Results: Cartilage thickness and circularity index increased in study group, especially circularity index increased markedly after 6 months (T 24 ) and this index was higher than that in the control group at all time of study (p < 0.05). Conclusion: Knee cartilage had a good recovery after treatment with AASC. * Keywords: Knee osteoarthritis; Autologous adipose stem cells; Cartilage restoration; MRI. INTRODUCTION regulation and differentiation into cartilage cells. Furthermore, with its endocrine Osteoarthritis is a common bone and mechanism, adipose stem cell can protect joint disease. It is considered as a leading joint cartilage from destruction and re-initiation cause of pain and disability in older of precursor cells. According to the findings people in Vietnam and many countries of clinical studies, AASC therapy in OA around the world. There was over 27 treatment significantly improved the million OA patients in the US in 2010 and degree of joint pain, significant rehabilitation this number in the UK was over 8 million of joint mobility, especially injured cartilage people [2]. Knee is the most common joint recovery [5]. In Vietnam, application of suffering from OA. Pain and dysfunction AASC in treatment of OA has marked the related to OA badly affected the quality of initial pilot phase with short follow-up and life, limited ability of working and routine inconsistent evaluation of treatment effect. activities of patients. In recent years, Therefore, we carried out this study with a AASC therapy has opened a new trend in view to: Evaluating the cartilage restoration treatment of OA. Adipose stem cells have on MRI of the method using AASC in important characteristics such as immune treatment of OA after 12 months. * 103 Hospital ** Vietnam Military Medical University Corresponding author: Ta Viet Hung (hungtv103@gmail.com) Date received: 18/07/2017 Date accepted: 16/08/2017 144
2. Journal of military phrmaco-medicine n O7-2017 SUBJECTS AND METHODS A prospective, cross-sectional descriptive, comparative randomized controlled study. 1. Subjects. * Techniques: 84 patients were diagnosed with primary knee OA following to ACR 1991 standard; - AASC was collected from abdominal stage I-II following to Kellgren-Lawrence fat tissue aspiration, isolation and activation classification [1]. All patients were treated at by autologous platelet-rich plasma and the Department of Joints and Endocrinology, monochromatic laser light. Military Hospital 103 from June 2014 to - Injection of activated adipose stem December 2015. Patients were randomly cell into knee joints in study group and divided into 2 groups: study group: sodium hyaluronate in control group: In 42 patients (84 joints) were treated with the treatment process, each patient was AASC with 3 injections each 2-month apart. given 3 injections, each 2-month apart. Control group: 42 patients (84 joints) were The number of injected cells per patient injected with 3 doses of sodium hyaluronate was approximately equal, about 20 x 10 6 into knee, each 2-monthapart, too. cells/joint. Excluded from the study those patients - Evaluation of MRI results: T 0 (before who did not agree to continue the study; injection), after 24 weeks (T 24 ) and after not enough study data; patients with 48 weeks (T 48 ). Morphometric analysis of coagulopathy; anesthetic allergic; heart knee cartilage including femur cartilage and and lung diseases, kidney failure, severe tibia cartilage were run by US Department liver failure. of Health Image-J software. The steps were 2. Methods. as follows: * Study design: Figure 1: Cartilage injury analysis on MRI using Image-J software. + From the patient's MRI image ( figure 1A ), the analyzed cartilage was cut out (figure 1B ). 145
3. Journal of military parmaco-medicine n 07-2017 Set the light signal threshold so that the - Circularity: entire solid bone, spongy bone and soft tissue of joints become the background signal. Then deleted the background to retain the analyzed cartilage ( figure 1C ), * Statistical analysis: each of which measures as follows: The study was approved by the Ethics - Center cartilage thickness (mm). Council before the research activities were - Area of cartilage in the central section conducted. The data were processed using (cm 2). SPSS 16.0. RESULTS Table 1: Changing the central cartilage thickness at medial condyle of femur on MRI at monitoring time (mm). Monitoring time Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 3.83 ± 0.44 3.80 ± 0.51 > 0.05 (2) T24 4.00 ± 0.44 3.87 ± 0.52 > 0.05 (3) T48 3.88 ± 0.43 3.83 ± 0.43 > 0.05 p2,1 0.05 p2,1 > 0.05, p 3,2 > 0.05 p p3,1 > 0.05 p3,1 > 0.05 At the medial condyle of femur, the study group had a thicker cartilage than the control group; however, the difference was not statistically significant. The study group reached the highest cartilage thickness at T 24 (after 6 months), it was significantly higher than pretreatment (p < 0.05). Table 2: Changing the central cartilage thickness at lateral condyle of femur on MRI at monitoring time (mm). Monitoring time Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 3.87 ± 0.38 3.88 ± 0.53 > 0.05 (2) T24 4.0 ± 0,39 3.85 ± 0.53 > 0.05 (3) T48 3.94 ± 0.38 3.82 ± 0.52 > 0.05 p2,1 0.05 p2,1 > 0.05, p 3,2 > 0.05 p p3,1 > 0.05 p3,1 > 0.05 At the lateral condyle of femur, the study group had a thicker cartilage than the control group. At the same time, the study group reached the highest cartilage thickness at T 24 , it was significantly different with pre-treatment (p < 0.05). 146
4. Journal of military phrmaco-medicine n O7-2017 Table 3: Changing the central cartilage thickness at medial condyle of tibia on MRI at monitoring time (mm). Monitoring time Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 3.91 ± 0.43 3.83 ± 0.41 > 0.05 (2) T24 4.00 ± 0.44 3.80 ± 0.39 < 0.05 (3) T48 3.96 ± 0.44 3.79 ± 0.40 < 0.05 p2,1 > 0.05, p 3,2 > 0.05 p2,1 > 0.05, p 3,2 > 0.05 p p3,1 > 0.05 p3,1 > 0.05 At the medial condyle of tibia, the study group had a thicker cartilage than the control group; however, the difference was not statistically significant. Table 4: Changing the central cartilage thickness at lateral condyle of tibia on MRI at monitoring time (mm). Monitoring time Study group (n = 84 joints) Control group(n = 84 joints) p (1) T0 3.88 ± 0.45 3.85 ± 0.42 > 0.05 (2) T24 3.91 ± 0.46 3.81 ± 0.41 > 0.05 (3) T48 3.88 ± 0.46 3.81 ± 0.40 > 0.05 p2,1 > 0.05, p 3,2 > 0.05 p2,1 > 0.05, p 3,2 > 0.05 p p3,1 > 0.05 p3,1 > 0.05 At the lateral condyle of femur, the study group had a thicker cartilage than the control group; however, the difference was not statistically significant. Table 5: Changing circularity index at medial condyle of femur on MRI at monitoring time. Monitoring times Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 0.0696 ± 0.007 0.068 ± 0.006 > 0.05 (2) T24 0.079 ± 0.007 0.07 ± 0.0075 < 0.001 (3) T48 0.077 ± 0.007 0.068 ± 0.007 < 0.001 p2,1 0.05 p2,1 > 0.05, p 3,2 > 0.05 p p3,1 0.05 At the medial condyle of femur, the study group had an increasing circularity index during the study, while the circularity index was significantly higher than that in the control group at both post-treatment points (p < 0.001). 147
5. Journal of military parmaco-medicine n 07-2017 Table 6: Changing circularity index at lateral condyle of femur on MRI at monitoring time. Monitoring time Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 0.06 ± 0.0077 0.061 ± 0.009 > 0.05 (2) T24 0.069 ± 0.006 0.062 ± 0.007 < 0.001 (3) T48 0.068 ± 0.008 0.060 ± 0.01 < 0.001 p2,1 0.05 p2,1 > 0.05, p 3,2 > 0.05 p p3,1 0.05 At the lateral condyle of femur, the study group had an increasing circularity index during the study, while the circularity index was significantly higher than the control group at both post-treatment points (p < 0.001). Table 7: Changing circularity index at medial condyle of tibia on MRI at monitoring time. Monitoring time Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 0.12 ± 0.008 0.12 ± 0.013 > 0.05 (2) T24 0.124 ± 0.006 0.12 ± 0.01 < 0.001 (3) T48 0.121 ± 0.0078 0.114 ± 0.015 < 0.001 p2,1 0.05 p2,1 > 0.05, p 3,2 < 0.01 p p3,1 < 0.01 p3,1 < 0.01 At the medial condyle of tibia, the study group had a significantly higher circularity index than the control group at both post-treatment points (p < 0.001). In the study group, the thickness of cartilage increased compared with before treatment, while the control group progressively decreased. Table 8: Changing circularity index at lateral condyle of tibia on MRI at monitoring time. Monitoring time Study group (n = 84 joints) Control group (n = 84 joints) p (1) T0 0.112 ± 0.0097 0.110 ± 0.011 > 0.05 (2) T2 4 0.119 ± 0.01 0.110 ± 0.01 < 0.01 (3) T48 0.117 ± 0.009 0.10 ± 0.009 < 0.01 p2,1 0.05 p2,1 > 0.05, p 3,2 < 0.01 p p3,1 < 0.01 p3,1 < 0.01 At the lateral condyle of tibia, the study group had a significantly higher circularity index than the control group at both post-treatment points (p < 0.001). In the study group, the thickness of cartilage increased compared with pre-treatment while the control group progressively decreased. 148
6. Journal of military phrmaco-medicine n O7-2017 DISCUSSION before treatment, however, the difference was not statistically significant ( tables 1 to To assess cartilage damage, some 4). Meanwhile, the circularity index methods can be taken respectively such as: increased in group which were treated by ultrasound, MRI, endoscopic and cartilage stem cell showed statistical significance histopathology. Each evaluation method compared to pre-treatment and control has its own vulnerability classification, group (p < 0.05). The results also showed however all of them are relative. In order that the circularity index was statistically to follow and evaluate changes in cartilage significant different in the same study in this new treatment, we selected patients group who were injected with adipose with early degenerative lesions and used tissue (TGA) during the follow-up period the US Department of Health Image-J and after 6 months (T 24 ). However, at the software to analyze the morphology of th 12 month (T 48 ), the index decreased knee cartilage. The examined sites included (table 5 to 8 ). This may be related to the femur cartilage and tibia cartilage through self-life time of new differentiated cartilage, several indexes such as cartilage thickness which will be degenerated and disappeared and circularity index. Cartilage thickness after a period of time. The research by Bui were measured at the center, front and Hong Thien Khanh et al (2014) through back of the femur cartilage and at the MRI analysis showed that the cartilage center of tibia cartilage. In patients with layers were partially regenerated at the knee OA, the cartilage usually damages damaged sites and thickened after the body's most affected areas, including 6 months of treatment [2]. According to the the central cartilage. Considering the central study by Pak (2011) in two clinical cases: cartilage thickness of the cartilage help to 70-year-old female and 79-year-old male evaluate the effect of knee OA treatment OA patients found that at week 12 th , by autologous adipose stem cell injection. the thickness of the cartilage at the front The circularity Index is a reliable measure of femur significantly increased. This of cartilage wear. In knee cartilage of OA improvement has been suggested by the patients, the cartilage surface is damaged authors through two main mechanisms: leading to reduce smoothness and increase (i) differentiation into cartilage tissue of the cartilage's circumference more than AASC at the injured sites of patients; normal cartilage, so the circularity index (ii) addition of growth factors such as TGF β, decreases. Thus, in our study, we used FGF, IGF, and PDGF [5]. Jo et al (2014) this indicator to monitor the extent of treated OA patient by injection of articular cartilage, thereby evaluating the mesenchymal stem cell from autologous effectiveness of the therapy. fat tissue into joints for 18 patients. MRI After examining in detail, the results images showed that the size of the damaged showed that in the group treated with cartilage decreased from 497.9 ± 29.7 mm 2 stem cell, changes in cartilage thickness down to 297.9 ± 51.2 mm 2 at the center such as femur cartilage, central tibia of the femur in high dose injection group, cartilage after treatment was higher than a 40% decrease was shown (p = 0.004). 149
7. Journal of military parmaco-medicine n 07-2017 Meanwhile, at the center of the tibia cartilage, REFERENCES the cartilage size of the injured cartilage decreased from 333.2 ± 51.2 mm 2 down 1. Tr ần Ng ọc Ân, Nguy ễn Th ị Ng ọc Lan, to 170.6 ± 48.2 mm 2, a 49% decrease Nguy ễn Mai H ồng . Thoái hóa kh ớp g ối. Phác (p < 0.01). In the high-dose group, the đồ ch ẩn đoán và điều tr ị các b ệnh c ơ x ươ ng cartilage volume increased gradually after kh ớp th ường g ặp. Nhà xu ất b ản Giáo d ục Vi ệt 6 months in both center cartilage of femur Nam. 2013, tr.178-184. and tibia: 3313.7 ± 304.1 mm 3 to 3780.6 ± 2. Khanh Hong Thien Bui et al. Symptomatic 284.4 mm 3, 14% increase (p = 0.044) and knee OA treatment using autologous adipose 1157.5 ± 145.8 mm 3 to 1407.7 ± 150.5 derived stem cells and platelet-rich plasma: a mm 3, 22% increase (p = 0.047) [4]. clinical study. Biomedical Research and Therapy. 2014, 1 (1), pp.2-8. CONCLUSION 3. Fransen M, Bridgett L, March L et al. Knee cartilage showed a good restoration The epidemiology of osteoarthritis in Asia. after treatment with AASC. Cartilage International Journal of Rheumatic Diseases. thickness and circularity index increased. 2011, 14 (2), pp.113-121. The circularity index was the best after 4. Jo C.H et al. Intra-articular injection of 6 months of treatment (T 24 ). The medium mesenchymal stem cells for the treatment of score in medial and lateral condyle of femur OA of the knee: a proof-of-concept clinical after 6 months of treatment was 0.079 and trial. Stem Cells. 2014, 32 (5), pp.1254-1266. 0.069, respectively and this value in 5. Pak J. Regeneration of human bones medial and lateral condyle of tibia was 0.124 hip osteonecrosis and human cartilage in and 0.119, respectively. The circularity index knee OA with autologous adipose-tissue- increased markedly after treatment and higher derived stem cells: a case series. Journal of than control group at all time (p < 0.05). Medical Case Reports. 2011, 5, p.296. 150