Orthopedics (general)

Pak J, Lee JH, Park KS, Park M, Kang LW, Lee SH. 2017.
»Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications.«
J Biomed Sci. 24 (1), 31. January

Liu Y, Zhang Z, Zhang C, et al. 2016.
»Adipose-derived stem cells undergo spontaneous osteogenic differentiation in vitro when passaged serially or seeded at low density.«
Biotech Histochem. 91 (5)

Oshita K, Yamaoka K, Udagawa N, et al. 2011.
»Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production.«
Arthritis Rheum. 63 (6)


Orthopedics (osteoarthritis)

Pak J, Lee JH, Kartolo WA, and Lee SH. 2016.
»Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications.«
Biomed Res Int.

Van Lent P, Schelbergen R, Huurne MT, et al. 2013.
»Synovial Activation in Experimental OA Drives Rapid Suppressive Effects of Adipose-Derived Stem Cells after Local Administration and Protects Against Development of Ligament Damage.«
Ann Rheum Dis. 72 (Suppl 3)

Erickson GR, Gimble JM, Franklin DM, Rice HE, Awad H, and Guilak F. 2003.
»Chondrogenic Potential of Adipose Tissue-Derived Stromal Cells in Vitro and in Vivo.«
Biochem Biophys Res Commun. 290 (2)

Sciarretta, F. 2013.
»Adipose tissue stromal vascular fraction: A new method for it’s regenerative application in one step chondral defect repair.«
Journal of Science and Medicine in Sport 16 (62)

Sciarretta, FV, and C Ascani. 2015.
»Adipose Tissue and Progenitor Cells for Cartilage Formation.«
Sports Injuries: Prevention, 10. June

Freitag J, Li D, Wickham J, Shah K, Tenen A. 2017.
»Effect of autologous adipose-derived mesenchymal stem cell therapy in the treatment of a post-traumatic chondral defect of the knee.«
BMJ Case Rep.

Freitag J, Shah K, Wickham J, Boyd R, Tenen A. 2017.
»The effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans – a case study.«
BMC Musculoskelet Disord. 18 (1)

Freitag J, Ford J, Bates D, et al. 2015.
»Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: Design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal stem cell injections.«
BMJ Open. 5 (12)


Orthopedics (osteoarthritis) continued

Jang Y, Koh YG, Choi YJ, Kim SH, Yoon DS, Lee M, and Lee JW. 2015.
»Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration.«
Vitr Cell Dev Biol – Anim. 51 (2), February

Zhang, Jinxin, Chunyan Du, Weimin Guo, Pan Li, Shuyun Liu, Zhiguo Yuan, Jianhua Yang, Sun Xun, Yin Heyong, Guo Quanyi, Zhou Chenfu. 2017.
»Adipose Tissue-Derived Pericytes for Cartilage Tissue Engineering.«
Current Stem Cell Research & Therapy 12 (6)

Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. 2008.
»Increased Knee Cartilage Volume in Degenerative Joint Disease using Percutaneously Implanted, Autologous Mesenchymal Stem Cells.«
Pain Physician, 11 (3), May

Pak J. 2011.
»Regeneration of Human Bones in Hip Osteonecrosis and Cartilage in Knee Osteoarthritis with Autologous Adipose Tissue-derived Stem Cells in Human – a series of case reports.«
J Med Case Rep. 5 (296)

Jo CH, Lee YG, Shin WH, et al. 2014.
»Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial.«
Stem Cells. 32 (5)

Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. 2015.
»Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis.«
Knee Surg Sports Traumatol Arthrosc. 23 (5)

Michalek J, Moster R, Lukac L, et al. 2015.
»Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis.«
Cell Transplant. January 20

Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, Fini M, Giardino R, Facchini A, and Grigolo B. 2013.
»Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model.«
Arthritis Research & Therapy, 15 (1)

Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V, and Jacobs CR. 2008.
»Buffered Platelet-Rich Plasma Enhances Mesenchymal Stem Cell Proliferation and Chondrogenic Differentiation.«
Tissue Eng Part C Methods. 15 (3), 10. February

Van Pham P, Hong-Thien Bui K, Quoc Ngo D, Tan Khuat L, and Kim Phan N. 2013.
»Transplantation of Nonexpanded Adipose Stromal Vascular Fraction and Platelet-Rich Plasma for Articular Cartilage Injury Treatment in Mice Model.«
J Med Eng.


Orthopedics (spine)

Piccirilli, Manolo, Catia P Delfinis, Antonio Santoro, and Maurizio Salvati. 2017.
»Mesenchymal stem cells in lumbar spine surgery: a single institution experience about red bone marrow and fat tissue derived MSCs.«
Journal of neurosurgical sciences, 6. April

Hansraj Kenneth. K. 2016.
»Stem cells in spine surgery.«
Surgical Technology International.

Schroeder J, Kueper J, Leon K, Liebergall M. 2015.
»Stem cells for spine surgery.«
World J Stem Cells. 7 (1), 26. January



Arthroscopy. 2017 Mar;33(3):659-670.e1. doi: 10.1016/j.arthro.2016.09.024. Epub 2016 Dec 22.
Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled
Dai WL1, Zhou AG1, Zhang H1, Zhang J2.
Author information:
Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:



To use meta-analysis techniques to evaluate the efficacy and safety of platelet-rich plasma (PRP) injections for the treatment knee
of osteoarthritis (OA).
We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane database through April 2016 to
identify Level I randomized controlled trials that evaluated the clinical efficacy of PRP versus control treatments for knee OA.
The primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores.
The primary outcomes were compared with their minimum clinically important differences (MCID)-defined as the smallest
difference perceived as important by the average patient.
We included 10 randomized controlled trials with a total of 1069 patients. Our analysis showed that at 6 months postinjection,
PRP and hyaluronic acid (HA) had similar effects with respect to pain relief (WOMAC pain score) and functional improvement
(WOMAC function score, WOMAC total score, International Knee Documentation Committee score, Lequesne score). At 12
months postinjection, however, PRP was associated with significantly better pain relief (WOMAC pain score, mean difference
-2.83, 95% confidence interval [CI] -4.26 to -1.39, P = .0001) and functional improvement (WOMAC function score, mean
difference -12.53, 95% CI -14.58 to -10.47, P  < .00001; WOMAC total score, International Knee Documentation Committee score,
Lequesne score, standardized mean difference 1.05, 95% CI 0.21-1.89, P = .01) than HA, and the effect sizes of WOMAC pain
and function scores at 12 months exceeded the MCID (-0.79 for WOMAC pain and -2.85 for WOMAC function score). Compared
with saline, PRP was more effective for pain relief (WOMAC pain score) and functional improvement (WOMAC function score)
at 6 months and 12 months postinjection, and the effect sizes of WOMAC pain and function scores at 6 months and 12 months
exceeded the MCID. We also found that PRP did not increase the risk of adverse events compared with HA and saline.
Current evidence indicates that, compared with HA and saline, intra-articular PRP injection may have more benefit in pain relief
and functional improvement in patients with symptomatic knee OA at 1 year postinjection.
Level I, meta-analysis of Level I studies.
Copyright © 2016. Published by Elsevier Inc.



Arthroscopy. 2013 Dec;29(12):2037-48. doi: 10.1016/j.arthro.2013.09.006.
The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis.
Khoshbin A1, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D, Gandhi R, Takhar K, Lum G, Chahal J.
Author information:
University of Toronto Orthopaedic Sports Medicine Program, Women’s College Hospital, Toronto, Ontario, Canada; The Hospital for Sick Children, Toronto, Ontario, Canada.



The purpose of this systematic review was to synthesize the available Level I and Level II literature on platelet-rich plasma (PRP) as a therapeutic intervention in the management of symptomatic knee osteoarthritis (OA).
A systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, PubMed, and www.clinicaltrials.gov was performed to identify all randomized controlled trials and prospective cohort studies that evaluated the clinical efficacy of PRP versus a control injection for knee OA. A random-effects model was used to evaluate the therapeutic effect of PRP at 24 weeks by use of validated outcome measures (Western Ontario and McMaster Universities Arthritis Index, visual analog scale for pain, International Knee Documentation Committee Subjective Knee Evaluation Form, and overall patient satisfaction).
Six Level I and II studies satisfied our inclusion criteria (4 randomized controlled trials and 2 prospective nonrandomized studies). A total of 577 patients were included, with 264 patients (45.8%) in the treatment group (PRP) and 313 patients (54.2%) in the control group (hyaluronic acid [HA] or normal saline solution [NS]). The mean age of patients receiving PRP was 56.1 years (51.5% male patients) compared with 57.1 years (49.5% male patients) for the group receiving HA or NS. Pooled results using the Western Ontario and McMaster Universities Arthritis Index scale (4 studies) showed that PRP was significantly better than HA or NS injections (mean difference, -18.0 [95% confidence interval, -28.8 to -8.3]; P < .001). Similarly, the International Knee Documentation Committee scores (3 studies) favored PRP as a treatment modality (mean difference, 7.9 [95% confidence interval, 3.7 to 12.1]; P < .001). There was no difference in the pooled results for visual analog scale score or overall patient satisfaction. Adverse events occurred more frequently in patients treated with PRP than in those treated with HA/placebo (8.4% v 3.8%, P = .002).
As compared with HA or NS injection, multiple sequential intra-articular PRP injections may have beneficial effects in the treatment of adult patients with mild to moderate knee OA at approximately 6 months. There appears to be an increased incidence of nonspecific adverse events among patients treated with PRP.
Level II, systematic review of Level I and II studies.


J Orthop Surg Res. 2017 Jan 23;12(1):16. doi: 10.1186/s13018-017-0521-3.
The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis:
systematic review and meta-analysis of randomized controlled trials.
Shen L1, Yuan T1, Chen S2, Xie X3, Zhang C1.
Author information:
Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital affiliated to Shanghai Jiaotong University School of
Medicine, 600 Yishan Road, Shanghai, 200233, China.
Section of Clinical Epidemiology, Institute of Orthopaedic Traumatology affiliated to Shanghai Jiaotong University, 600 Yishan
Road, Shanghai, 200233, China.
Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital affiliated to Shanghai Jiaotong University School of
Medicine, 600 Yishan Road, Shanghai, 200233, China. xuetaoxie@163.com.



Quite a few randomized controlled trials (RCTs) investigating the efficacy of platelet-rich plasma (PRP) for treatment of knee
osteoarthritis (OA) have been recently published. Therefore, an updated systematic review was performed to evaluate the
temporal effect of PRP on knee pain and physical function.
Pubmed, Embase, Cochrane library, and Scopus were searched for human RCTs comparing the efficacy and/or safety of PRP
infiltration with other intra-articular injections. A descriptive summary and quality assessment were performed for all the
studies finally included for analysis. For studies reporting outcomes concerning Western Ontario and McMaster Universities
Arthritis Index (WOMAC) or adverse events, a random-effects model was used for data synthesis.
Fourteen RCTs comprising 1423 participants were included. The control included saline placebo, HA, ozone, and corticosteroids.
The follow-up ranged from 12 weeks to 12 months. Risk of bias assessment showed that 4 studies were considered as moderate
risk of bias and 10 as high risk of bias. Compared with control, PRP injections significantly reduced WOMAC pain subscores at
3, 6, and 12 months follow-up (p = 0.02, 0.004, <0.001, respectively); PRP significantly improved WOMAC physical function
subscores at 3, 6, and 12 months (p = 0.002, 0.01, <0.001, respectively); PRP also significantly improved total WOMAC scores at
3, 6 and 12 months (all p < 0.001); nonetheless, PRP did not significantly increased the risk of post-injection adverse events
(RR, 1.40 [95% CI, 0.80 to 2.45], I 2  = 59%, p = 0.24).
Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported
function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and
PROSPERO CRD42016045410 . Registered 8 August 2016.
PMCID: PMC5260061 Free PMC Article



J Biomed Mater Res B Appl Biomater. 2017 Aug;105(6):1536-1543. doi: 10.1002/jbm.b.33688. Epub 2016 Apr 29.
Intra-articular Injection of platelet-rich fibrin releasates in combination with bone marrow-derived mesenchymal
stem cells in the treatment of articular cartilage defects: An in vivo study in rabbits.
Wu CC1,2, Sheu SY3,4,5, Hsu LH1,2, Yang KC6, Tseng CC7, Kuo TF7,8.
Author information:
Department of Orthopedics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 10002,
Department of Orthopedics, En Chu Kong Hospital, New Taipei City, 23702, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
Department of Integrated Chinese and Western Medicine, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan.
Department of Occupational Therapy, Asia University, Taichung, 41354, Taiwan.
School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan.
Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan.
Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung, 41354, Taiwan.



The use of mesenchymal stem cells (MSCs), which can be differentiated into chondrocytes under specific conditions, has been
proposed for the treatment of cartilage defects. Blood-derived platelet-rich fibrin releasate (PRFr), which is rich in growth
factors and cytokines, may improve cartilage regeneration. In this study, the therapeutic effects of PRFr in combination with
bone marrow-derived MSCs for articular cartilage regeneration were evaluated in a rabbit model. Critical osteochondral defects
were surgically created in the femoral condyle of the rabbits, and 3 × 106 of MSCs, 0.8 mL of PRFr, or a combination of MSCs
and PRFr were injected intra-articularly and one week after first administration. The animals were sacrificed 12 weeks
postoperatively, and the regenerated cartilages were assessed by gross inspection and histological examination. No
treatment-related adverse events were noted in any of the rabbits. The size of the defect decreased and the volume of
regenerated cartilage increased in the medial femoral condyles of the MSCs + PRFr group. Relative to the MSCs or PRFr group,
histological examination demonstrated that the MSCs + PRFr group had thicker hyaline-like cartilaginous tissue with normal
glycosaminoglycan production. Grading scores revealed that MSCs + PRFr injection had better matrix, cell distribution, and
surface indices than other groups. The results showed that intra-articular injections of MSCs + PRFr into the knee can reduce
cartilage defects by regenerating hyaline-like cartilage without adverse events. This approach may provide an alternative
method of autologous chondrocyte implantation to repair cartilage defects with an unlimited source of cells and releasate.
© 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1536-1543, 2017.