For helsepersonell

Bibliografi av vitenskapelig dokumentasjon for terapeutiske behandlinger som tilbys av Regenerative.

Legene ved Regenerative er overleger med spesialkompetanser i ortopedisk kirurgi og smertebehandling. Under finner du litteraturgjennomgang av vitenskapelige publikasjoner dokumenterer bruk av PRP, iPRF og ADSC.



Behandlinger for ledd- og senesmerter ved Regenerative tar sikte på å forbedre funksjonen, redusere smerte og regenerere berørte ledd. De anvendte teknikkene er basert på sunne vitenskapelige prinsipper som har blitt godt dokumentert i medisinsk litteratur. Regenerative behandlinger bruker ikke noen kunstige tilsetningsstoffer eller stoffer for å oppnå de ønskede effektene. Behandlingene er basert på å oppnå høye konsentrasjoner av vekstfaktorer og cytokiner avledet fra autologt blod eller fettvev. Disse injiseres deretter under kontrollerte forhold i passende fellesrom.

SKIN – iPRF referanser og abstrakter

Tissue Eng Part B Rev. 2017 Feb;23(1):83-99. doi: 10.1089/ten.TEB.2016.0233. Epub 2016 Oct 10.
Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review.
Miron RJ1, Fujioka-Kobayashi M1,2,3, Bishara M4, Zhang Y5, Hernandez M1, Choukroun J6.
Author information:
1 Department of Periodontology, Nova Southeastern University , Fort Lauderdale, Florida.
2 Cranio-Maxillofacial Surgery, Bern University Hospital , Inselspital, Bern, Switzerland .
3 Department of Oral Surgery, Clinical Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan .
4 West Bowmanville Family Dental , Ontario, Canada .
5 Department of Oral Implantology, University of Wuhan , Wuhan, China .
6 Pain Clinic , Nice, France.



The growing multidisciplinary field of tissue engineering aims at predictably regenerating, enhancing, or replacing damaged or missing tissues for a variety of conditions caused by trauma, disease, and old age. One area of research that has gained tremendous awareness in recent years is that of platelet-rich fibrin (PRF), which has been utilized across a wide variety of medical fields for the regeneration of soft tissues. This systematic review gathered all the currently available in vitro, in vivo, and clinical literature utilizing PRF for soft tissue regeneration, augmentation, and/or wound healing. In total, 164 publications met the original search criteria, with a total of 48 publications meeting inclusion criteria (kappa score = 94%). These studies were divided into 7 in vitro, 11 in vivo, and 31 clinical studies. In summary, 6 out of 7 (85.7%) and 11 out of 11 (100%) of the in vitro and in vivo studies, respectively, demonstrated a statistically significant advantage for combining PRF to their regenerative therapies. Out of the remaining 31 clinical studies, a total of 8 reported the effects of PRF in a randomized clinical trial, with 5 additional studies (13 total) reporting appropriate controls. In those clinical studies, 9 out of the 13 studies (69.2%) demonstrated a statistically relevant positive outcome for the primary endpoints measured. In total, 18 studies (58% of clinical studies) reported positive wound-healing events associated with the use of PRF, despite using controls. Furthermore, 27 of the 31 clinical studies (87%) supported the use of PRF for soft tissue regeneration and wound healing for a variety of procedures in medicine and dentistry. In conclusion, the results from the present systematic review highlight the positive effects of PRF on wound healing after regenerative therapy for the management of various soft tissue defects found in medicine and

Facial Plast Surg. 2009 Nov;25(4):270-6. doi: 10.1055/s-0029-1242033. Epub 2009 Nov 18.
Applications of platelet-rich fibrin matrix in facial plastic surgery.
Sclafani AP1.
Author information:
Director of Facial Plastic Surgery, The New York Eye and Ear Infirmary, New York, New York 10003, USA.



Platelet concentrates enjoyed some clinical popularity in facial plastic surgery several years ago. However, interest waned
due to expense, amount of blood required, equipment, space, and staff needed, and lack of clinically significant benefit. A
novel, simple method of preparing an autologous platelet derivative (Selphyl; Aesthetic Factors, Princeton, NJ) allows rapid
and inexpensive generation of a platelet-rich fibrin matrix (PRFM) that can be used to enhance healing after facial procedures
as well as to rejuvenate the face without tissue manipulation. PRFM provides autologous, natural, but concentrated platelet
growth factor release and stimulation of surrounding tissue. This article describes its use for cosmetic facial applications.
PMID: 19924600 [Indexed for MEDLINE



J Cosmet Dermatol. 2010 Mar;9(1):66-71. doi: 10.1111/j.1473-2165.2010.00486.x.
Platelet-rich fibrin matrix for improvement of deep nasolabial folds.
Sclafani AP1.
Author information:
Division of Facial Plastic Surgery, The New York Eye & Ear Infirmary, New York, New York 10003, USA.



Dermal augmentation continues to grow as an aesthetic facial procedure. Many exogenous filler materials rely on an autologous
fibrotic response for volume augmentation.
To evaluate the efficacy of a single injection of autologous platelet-rich fibrin matrix (PRFM) for the correction of deep nasolabial
folds (NLFs).
Whole blood was obtained from 15 adults, and an activated autologous PRFM produced using a proprietary system (Selphyl;
Aesthetic Factors, Inc., Wayne, NJ, USA) was then injected into the dermis and immediate subdermis below the NLFs. Subjects
were photographed before and after treatment; NLFs were rated by the treating physician before and after treatment using the
Wrinkle Assessment Scale (WAS) and patients rated their appearance at each post-treatment visit using the Global Aesthetic
Improvement Scale. Patients were evaluated at 1, 2, 6, and 12 weeks after treatment.
All patients were treated to maximal (no over-) correction, with a mean reduction in WAS score of 2.12 +/- 0.56. At 1 week after
treatment, this difference was 0.65 +/- 0.68, but rose to 0.97 +/- 0.75, 1.08 +/- 0.59, and 1.13 +/- 0.72 at 2, 6, and 12 weeks after
treatment, respectively (P < 0.001). No patient noted any fibrosis, irregularity, hardness, restricted movement, or lumpiness.
PRFM can provide significant long-term diminution of deep NLFs without the use of foreign materials. PRFM holds significant
potential for stimulated dermal augmentation.



Aesthetic Plast Surg. 2015 Aug;39(4):495-505. doi: 10.1007/s00266-015-0504-x. Epub 2015 Jun 5.
Platelet Preparations for Use in Facial Rejuvenation and Wound Healing: A Critical Review of Current Literature.
Sclafani AP1, Azzi J.
Author information:
Department of Otolaryngology, Weill Cornell Medical College, 1305 York Avenue, 5th Floor, New York, NY, 10021, USA,

Comment in
– Use of Platelet Preparations in Facial Rejuvenation and Wound Healing Remains Unproven. [Aesthetic Plast Surg. 2016]



In facial plastic surgery, the potential for direct delivery of growth factors from platelet preparations has been of particular
interest for use in facial rejuvenation, recovery after facial surgery, and wound healing. A literature search was conducted
through PubMed for the terms PRP, PRFM, platelet-rich plasma, platelet-rich fibrin matrix, platelet preparations, platelet
therapy, growth factors, platelet facial, platelet facial rejuvenation, platelet wound healing, platelet plastic surgery. Articles
pertaining to the use of platelet preparations in facial surgery and wound healing in plastic surgery after 2001 were included.
Thirteen in vitro studies showed use of platelet-rich plasma (PRP) and platelet-rich fibrin matrix (PRFM) had a significant
effect on cellular activity. Twenty-four out of 28 animal studies exhibited favorable results with use of a platelet preparation,
including five of six studies that showed enhanced fat graft survival with addition of a platelet preparation. Twenty-three
case series and clinical trials were identified, only two of which showed no differences. Twenty-one reported favorable
results with use of various platelet preparations. A total of 47 studies used PRP, four studies evaluated Leukocyte-rich PRP,
and fourteen studies used PRFM. The vast majority of studies examined show a significant and measurable effect on cellular
changes, wound healing, and facial esthetic outcomes with use of platelet preparations, both topical and injectable. One must
also consider possible publication bias against null results that may have had an influence on the data that were available for
review. However, the preponderance of studies suggests that platelet preparations might represent an as-of-yet untapped
adjunct in facial plastic surgery.

PMID: 26044392 [Indexed for MEDLINE]


Cicione, Claudia, Giuseppe Di Taranto, Marta Barba, Maria A. Isgrò, Alessio D’Alessio, Daniele Cervelli, Fabio V. Sciarretta, Sandro Pelo, Fabrizio Michetti, and Wanda Lattanzi. 2016.
»In vitro validation of a closed device enabling the purification of the fluid portion of liposuction aspirates.«
Plastic & Reconstructive Surgery, April

Gentile P, Scioli MG, Orlandi A, and Cervelli V. 2015.
»Breast Reconstruction with Enhanced Stromal Vascular Fraction Fat Grafting.«
Plast Reconstr Surg – Glob Open. 3 (6), June

Condé-Green A, Kotamarti VS, Sherman LS, Keith JD, Lee ES, Granick MS, Rameshwar P. 2016.
»Shift toward Mechanical Isolation of Adipose-derived Stromal Vascular Fraction: Review of Upcoming Techniques.«
Plast Reconstr surgery Glob open. 4 (9), September

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


Aesthetics (face)

Park Byung-Soon, Kyoung Ae Jang, Jong-Hyuk Sung, Jeong-Soo Park, Yong Hyun Kwon, Kea Jeong Kim, and Won-Serk Kim. 2008.
»Adipose-Derived Stem Cells and Their Secretory Factors as a Promising Therapy for Skin Aging.«
Dermatologic Surgery 34 (10), 4. July.

Dhong, Eun-Sang, Na-Hyun Hwang, Deok-Woo Kim, Gangaraju Rajashekhar, Brian
H. Johnstone, and Keith L. March. 2012.
»Morphologic Changes in Photodamaged Organotypic Human Skin Culture After Treatment of Autologous Adipose-Derived Stromal Cells.«
Journal of Craniofacial Surgery, May: 805-811.

Wei, Hua, Shi-Xing X Gu, Yi-Dan D Liang, Zhi-Jie J Liang, Hai Chen, Mao-Guang G Zhu, Fang-Tian T Xu, Ning He, Xiao-Juan J Wei, and Hong-Mian M Li. 2017.
»Nanofat-Derived Stem Cells with Platelet-Rich Fibrin Improve Facial Contour Remodeling and Skin Rejuvenation after Autologous Structural Fat Transplantation.«
Oncotarget 8 (40), 5. September 5

Spiekman M, van Dongen JA, Willemsen JC, Hoppe DL, van der Lei B, Harmsen MC. 2017.
»The power of fat and its adipose-derived stromal cells: emerging concepts for fibrotic scar treatment.«
J Tissue Eng Regen Med. 4 (7), 3. February

Gentile, Pietro, Barbara Angelis, Mehtap Pasin, Giulio Cervelli, Cristiano Curcio, Micol Floris, Camilla Pasquali, et al. 2014.
»Adipose-derived stromal vascular fraction cells and platelet-rich plasma: basic and clinical evaluation for cell-based therapies in patients with scars on the face.«
J Craniofac Surg. 25 (1), January

Spiekman, Maroesjka, Ewa Przybyt, Josée A A Plantinga, Susan Gibbs, Berend van der Lei, and Martin C Harmsen. 2014.
»Adipose Tissue-Derived Stromal Cells Inhibit TGF-β1-Induced Differentiation of Human Dermal Fibroblasts and Keloid Scar-Derived Fibroblasts in a Paracrine Fashion.«
Plastic and Reconstructive Surgery 134 (4), 3. October

Park B, Kim W. 2017.
»Adipose-Derived Stem Cells and Their Secretory Factors for Skin Aging and Hair Loss.«
Farage M., Miller K., Maibach H. (eds) Textbook of Aging Skin. Springer.

Borovikova AA, Ziegler ME, Banyard DA, et al. 2018.
»Adipose-Derived Tissue in the Treatment of Dermal Fibrosis.«
Ann Plast Surg. 1, January


Aesthetics (hair)

Park B, Kim W. 2017.
»Adipose-Derived Stem Cells and Their Secretory Factors for Skin Aging and Hair Loss.«
Farage M., Miller K., Maibach H. (eds) Textbook of Aging Skin. Springer.

Park, Byung-Soon, Won-Serk Kim, Joon-Seok Choi, Hyung-Ki Kim, Jong-Hyun Won, Fumio Ohkubo, and Hirotaro Fukuoka. 2010.
»Hair Growth Stimulated by Conditioned Medium of Adipose-Derived Stem Cells Is Enhanced by Hypoxia: Evidence of Increased Growth Factor Secretion.«
Biomedical Research 31 (1), February

ADIPOSE / PRF references and abstracts


Int Wound J. 2017 Feb;14(1):112-124. doi: 10.1111/iwj.12569. Epub 2016 Feb 1.
The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery.
Naderi N1,2, Combellack EJ1,2, Griffin M3, Sedaghati T3, Javed M1,2, Findlay MW4, Wallace CG5, Mosahebi A3,6, Butler PE6,
Seifalian AM3, Whitaker IS1,2.
Author information:
Reconstructive Surgery & Regenerative Medicine Group, Institute of Life Sciences (ILS), Swansea University Medical School,
Swansea, UK.
Welsh Centre for Burns & Plastic Surgery, ABMU Health Board, Swansea, UK.
UCL Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK.
Plastic & Reconstructive Surgery, Stanford University Medical Centre, Stanford, CA, USA.
Plastic & Reconstructive Surgery, Royal Devon & Exeter Hospital, Exeter, UK.
Department of Plastic Surgery, Royal Free NHS Foundation Trust, London, UK.



The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm
shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells
(iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically
highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine.
Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and
endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue.
Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and
differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in
plastic and reconstructive surgery.

PMID: 26833722


Methods Mol Biol. 2018;1773:107-122. doi: 10.1007/978-1-4939-7799-4_9.
Adipose-Derived Stromal Vascular Fraction Cells and Platelet-Rich Plasma: Basic and Clinical Implications for Tissue Engineering Therapies in Regenerative Surgery.
Gentile P1,2, Cervelli V3.
Author information:
Department of Plastic and Reconstructive Surgery, University of Rome “Tor Vergata”, Rome, Italy.
Catholic University, Tirane, Albania.
Department of Plastic and Reconstructive Surgery, University of Rome “Tor Vergata”, Rome, Italy.



Cell-based therapy and regenerative medicine offer a paradigm shift in regard to various diseases causing loss of substance or volume and tissue or organ damage. Recently, many authors have focused their attention on mesenchymal stem cells for their capacity to differentiate into many cell lineages. The most widely studied types are bone marrow mesenchymal stem cells and adipose derived stem cells (ADSCs), which display similar results. Based on the literature, we believe that the ADSCs offer advantages because of lower morbidity during the harvesting procedure. Additionally, platelet-rich plasma can be used in this field for its ability to stimulate tissue regeneration. The aim of this chapter is to describe ADSC preparation and isolation procedures, preparation of platelet-rich plasma, and the application of ADSCs in regenerative plastic surgery. We also discuss the mechanisms and future role of ADSCs in cell-based therapy and tissue engineering.

PMID: 29687384


Rev Laryngol Otol Rhinol (Bord). 2007;128(4):255-60.
[The relevance of Choukroun’s platelet rich fibrin (PRF) during facial aesthetic lipostructure (Coleman’s technique): preliminary results].
[Article in French]
Braccini F1, Dohan DM.
Author information:
AP-HP Hôpital Albert Chenevier-Henri Mondor, Département de Chirurgie Orale, 40 Rue de Mesly, 94000 Créteil, France.



To evaluate the interest of fibrin PRF clots, a concentrate of platelets and immune factors, for the optimization of the adipocyte graft according to the technique of facial lipostructure described by S. Coleman.
Between May 2005 and June 2006, 32 patients (7 men and 25 women) benefited from a Coleman lipostructure with the use of PRF. The average age was 59 years (39 to 72 years). Lipostructure was used alone in 22 patients and associated with a face lift and/or a blepharoplasty in 10 patients. Before the adipocyte graft, a mixture of PRF and greasy supernatant (resulting from the purification of the sample of adipocytes) is deposited on the zones to be grafted in the same way as for lipostructure. For 2 patients, the pretreatment of the site to be grafted with PRF was unilateral. Patients were followed-up for one year.
In this series, all the patients were satisfied with the result with minimal associated resorptions. No massive resorption requiring a resumption of lipostructure was noted. In the 2 patients treated with unilateral use of PRF, one notes a light asymmetry, the hemi-face treated with PRF appearing more stable than the side without PRF. No important residual oedema or echymosis were seen on the 3rd post-operative week.
By offering a matricial support to angiogenesis and by stimulating the proliferation of pre-adipocytes, the PRF could have a beneficial role on the cicatrization and the consolidation of an adipocyte graft. Further studies are necessary to validate the interest of the PRF during aesthetic lipostructures. The potential uses in plastic surgery of such a biomaterial, easy and fast to produce, without any overcost and with no risk, are very numerous and require from now on to be tested and validated methodically.


Stem Cell Res Ther. 2015 Nov 5;6:215. doi: 10.1186/s13287-015-0217-8.
Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness.
Tobita M1, Tajima S1, Mizuno H2.
Author information:
Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 1138421, Japan.
Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 1138421, Japan.



Because of their ease of isolation and relative abundance, adipose-derived mesenchymal stem cells (ASCs) are a particularly attractive autologous cell source for various therapeutic purposes. ASCs retain a high proliferation capacity in vitro and have the ability to undergo extensive differentiation into multiple cell lineages. Moreover, ASCs secrete a wide range of growth factors that can stimulate tissue regeneration. Therefore, the clinical use of ASCs is feasible. However, the potential of ASCs differs depending on the donor’s medical condition, including diseases such as diabetes. Recent studies demonstrated that ASCs from diabetic donors exhibit reduced proliferative potential and a smaller proportion of stem cell marker-positive cells. Therefore, to ensure the success of regenerative medicine, tissue engineering methods must be improved by the incorporation of factors that increase the proliferation and differentiation of stem/progenitor cells when autologous cells are used. Platelet-rich plasma (PRP), which contains high levels of diverse growth factors that can stimulate stem cell proliferation and cell differentiation in the context of tissue regeneration, has recently been identified as a biological material that could be applied to tissue regeneration. Thus, co-transplantation of ASCs and PRP represents a promising novel approach for cell therapy in regenerative medicine. In this review, we describe the potential benefits of adding PRP to ASCs and preclinical and clinical studies of this approach in various medical fields. We also discuss the mechanisms of PRP action and future cell-based therapies using co-transplantation of ASCs and PRP.
PMCID: PMC4635588 Free PMC Article



Orthopaedic references and abstracts


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 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.



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.