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Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

RETRACTED ARTICLE: Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis

Authors: Himanshu Bansal, Kristin Comella, Jerry Leon, Poonam Verma, Diwaker Agrawal, Prasad Koka, Thomas Ichim

Published in: Journal of Translational Medicine | Issue 1/2017

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Abstract

Background

Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet rich plasma (PRP) can be obtained from peripheral blood. We evaluated the safety and preliminary efficacy of administering SVF and PRP intra-articularly into patients with osteoarthritis grade 1 and 2.

Methods

A total of ten patients underwent a local tumescent liposuction procedure to remove approximately 100 ml of fat tissue from the abdomen. SVF was isolated using an enzyme digestion and resuspended in PRP for intra-articular injection in the knee. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and six-minute walk distance (6MWD) were used to evaluate clinical effects and included measure of patient’s subjective assessment of pain, joint mobility, and physical disability. WOMAC score, 6MWD and laboratory tests were repeated at 3 and 6 months and 1, 1.5 and 2 years. XRAY and MRI were completed at 1 year.

Results

The average total WOMAC score was 64 at baseline and significantly reduced to 52 at 3 months, 46 at 6 months, 42 at 1 year, 38 at 1.5 years, and 41 at 2 years. Patients walked an average of 1310 feet at baseline and demonstrated a statistically significant improvement at 3 and 6 months and 1, 1.5, and 2 years post treatment. Cartilage thickness as determined by MRI improved by at least 0.2 mm in six patients, was unchanged in two patients and decreased by at least 0.2 mm in two patients.

Conclusions

Overall, all of the patients were pleased with the treatment results. They reported a reduction in pain levels, especially after 3 months. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications reported.
Trial registration NCT03089762; Name of registry: http://​www.​clinicaltrials.​gov
Literature
1.
go back to reference Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697–707.CrossRef Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697–707.CrossRef
2.
go back to reference Sun HB. Mechanical loading, cartilage degradation and arthritis. Ann N Y Acad Sci. 2010;1211:37–50.CrossRef Sun HB. Mechanical loading, cartilage degradation and arthritis. Ann N Y Acad Sci. 2010;1211:37–50.CrossRef
3.
go back to reference Osteoarthritis: national clinical guideline for care and management in adults. London: Royal College of Physicians; 2008. Osteoarthritis: national clinical guideline for care and management in adults. London: Royal College of Physicians; 2008.
4.
go back to reference Altman RD, Hochberg MC, Moscowitz RW, Schnitzer T. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum. 2000;43:1905–15.CrossRef Altman RD, Hochberg MC, Moscowitz RW, Schnitzer T. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum. 2000;43:1905–15.CrossRef
5.
go back to reference Jordan KM, Arden NK, Doherty M. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the standing committee for international clinical studies including therapeutic trails (ESCISIT). Ann Rheum Dis. 2003;62:1145–55.CrossRef Jordan KM, Arden NK, Doherty M. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the standing committee for international clinical studies including therapeutic trails (ESCISIT). Ann Rheum Dis. 2003;62:1145–55.CrossRef
6.
go back to reference Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline. J Am Acad Orthop Surg. 2013;21:577–9.PubMed Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline. J Am Acad Orthop Surg. 2013;21:577–9.PubMed
7.
go back to reference Kirkley A, Birmingham TB, Litchfield RB, Giffin JR, Willits KR, Wong CJ, Feagan BG, Donner A, Griffin SH, D’Ascanio LM. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2008;359:1097–107.CrossRef Kirkley A, Birmingham TB, Litchfield RB, Giffin JR, Willits KR, Wong CJ, Feagan BG, Donner A, Griffin SH, D’Ascanio LM. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2008;359:1097–107.CrossRef
8.
go back to reference Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004;86:455–64.CrossRef Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004;86:455–64.CrossRef
9.
go back to reference Hematti P, Keating A. Mesenchymal stromal cells in regenerative medicine: a perspective. In: Hematti P, Keating A, editors. Mesenchymal stromal cells. Biology and clinical applications. New York: Humana Press; 2013. p. 3–16.CrossRef Hematti P, Keating A. Mesenchymal stromal cells in regenerative medicine: a perspective. In: Hematti P, Keating A, editors. Mesenchymal stromal cells. Biology and clinical applications. New York: Humana Press; 2013. p. 3–16.CrossRef
10.
go back to reference Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012;14:R3.CrossRef Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012;14:R3.CrossRef
11.
go back to reference Noth U, Ander F, Steinert I. Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol. 2008;4(7):371–80.CrossRef Noth U, Ander F, Steinert I. Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol. 2008;4(7):371–80.CrossRef
12.
go back to reference Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–5.CrossRef Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–5.CrossRef
13.
go back to reference Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–86.CrossRef Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–86.CrossRef
14.
go back to reference Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005;54:132–41.CrossRef Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005;54:132–41.CrossRef
15.
go back to reference Bunnell B. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;01:1249–60. Bunnell B. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;01:1249–60.
16.
go back to reference Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm CJ, Bovenkerk JE, Pell C, Johnstone B, Considine RV, March KL. The secretion of angiogenic and anti-apoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1291–8.CrossRef Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm CJ, Bovenkerk JE, Pell C, Johnstone B, Considine RV, March KL. The secretion of angiogenic and anti-apoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1291–8.CrossRef
17.
go back to reference Stan G, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol. 2001;189(1):54–63.CrossRef Stan G, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol. 2001;189(1):54–63.CrossRef
18.
go back to reference Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, Johnstone BH, March KL. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. 2008;102(1):77–85.CrossRef Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, Johnstone BH, March KL. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. 2008;102(1):77–85.CrossRef
19.
go back to reference Jang Y, Koh YG, Choi YJ, Kim SH, Yoon DS, Lee M, Lee JW. Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration. Vitro Cell Dev Biol Anim. 2015;51(2):142–50.CrossRef Jang Y, Koh YG, Choi YJ, Kim SH, Yoon DS, Lee M, Lee JW. Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration. Vitro Cell Dev Biol Anim. 2015;51(2):142–50.CrossRef
20.
go back to reference Aust I, Devlin B, Foster SJ, Halverson YD, Hicok K, du Laney T. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy. 2004;6:7–14.CrossRef Aust I, Devlin B, Foster SJ, Halverson YD, Hicok K, du Laney T. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy. 2004;6:7–14.CrossRef
21.
go back to reference Estes BT, Diekman BO, Gimble JM, Guilak F. Isolation of adipose-derived stem cells and their induction to a chondrogenic phenotype. Nat Protoc. 2010;5:1294–311.CrossRef Estes BT, Diekman BO, Gimble JM, Guilak F. Isolation of adipose-derived stem cells and their induction to a chondrogenic phenotype. Nat Protoc. 2010;5:1294–311.CrossRef
22.
go back to reference Koh YG, Jo SB. Mesenchymal stem cells injections improve symptoms of knee osteoarthritis. Arthroscopy. 2013;29(4):748–55.CrossRef Koh YG, Jo SB. Mesenchymal stem cells injections improve symptoms of knee osteoarthritis. Arthroscopy. 2013;29(4):748–55.CrossRef
23.
go back to reference van Lent PLEM, ven den Berg WB. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation? Arthritis Res Ther. 2013;15:112.CrossRef van Lent PLEM, ven den Berg WB. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation? Arthritis Res Ther. 2013;15:112.CrossRef
24.
go back to reference Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 2014;32:1254–66.CrossRef Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 2014;32:1254–66.CrossRef
25.
go back to reference Wang W, He N, Feng C, Liu V, Zhang L, Wang F, He J, Zhu T, Wang S, Qiao W, Li S, Zhou G, Zhang L, Dai C, Cao W. Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage. Int J Mol Sci. 2015;16:12076–91.CrossRef Wang W, He N, Feng C, Liu V, Zhang L, Wang F, He J, Zhu T, Wang S, Qiao W, Li S, Zhou G, Zhang L, Dai C, Cao W. Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage. Int J Mol Sci. 2015;16:12076–91.CrossRef
26.
go back to reference Michalek J, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, Capkova M, Chaloupka A, Darinskas A, Michalek J Sr, Kristek J, Travnik J, Jabandziev P, Cibulka M, Holek M, Jurik M, Skopalik J, Kristkova Z, Dudasova Z. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015. doi:10.3727/096368915X686760.CrossRefPubMed Michalek J, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, Capkova M, Chaloupka A, Darinskas A, Michalek J Sr, Kristek J, Travnik J, Jabandziev P, Cibulka M, Holek M, Jurik M, Skopalik J, Kristkova Z, Dudasova Z. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015. doi:10.​3727/​096368915X686760​.CrossRefPubMed
27.
go back to reference Bui KH, Duong TD, Nguyen TN, Nguyen TD, Le VT, Mai VT, Phan NL, Le DM, Ngoc NK, Phan PV. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomed Res Ther. 2014;1:2–8.CrossRef Bui KH, Duong TD, Nguyen TN, Nguyen TD, Le VT, Mai VT, Phan NL, Le DM, Ngoc NK, Phan PV. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomed Res Ther. 2014;1:2–8.CrossRef
28.
go back to reference Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012;21:2724–52.CrossRef Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012;21:2724–52.CrossRef
29.
go back to reference Mirsaidi A, Kleinhans KN, Rimann M, Tiaden AN, Stauber M, Rudolph KL, Richards PJ. Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice. J Tissue Eng Regen Med. 2012;6:378–90.CrossRef Mirsaidi A, Kleinhans KN, Rimann M, Tiaden AN, Stauber M, Rudolph KL, Richards PJ. Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice. J Tissue Eng Regen Med. 2012;6:378–90.CrossRef
31.
go back to reference Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005;84:434–9.CrossRef Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005;84:434–9.CrossRef
32.
go back to reference Bellamy N, Buchanan WW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.PubMed Bellamy N, Buchanan WW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.PubMed
33.
go back to reference Lequesne M, Brandt K, Bellamy N, Moskowitz R, Menkes CJ, Pelletier JP. Guidelines for testing slow acting drugs in osteoarthritis. J Rheumatol Suppl. 1994;41:65–71.PubMed Lequesne M, Brandt K, Bellamy N, Moskowitz R, Menkes CJ, Pelletier JP. Guidelines for testing slow acting drugs in osteoarthritis. J Rheumatol Suppl. 1994;41:65–71.PubMed
34.
go back to reference Schrama JC, Espehaug B, Hallan G, Engesaeter E. Risk of revision for infection in primary total hip and knee arthroplasty in patients with rheumatoid arthritis compared with osteoarthritis: a prospective, population-based study on 108,786 hip and knees joint arthroplasties from the Norwegian Arthoplasty Register. Arthritis Care Res. 2010;62:473–9.CrossRef Schrama JC, Espehaug B, Hallan G, Engesaeter E. Risk of revision for infection in primary total hip and knee arthroplasty in patients with rheumatoid arthritis compared with osteoarthritis: a prospective, population-based study on 108,786 hip and knees joint arthroplasties from the Norwegian Arthoplasty Register. Arthritis Care Res. 2010;62:473–9.CrossRef
35.
go back to reference Bernardo ME, Locatelli F, Fibbe WE. Mesenchymal stromal cells: a novel treatment modality for tissue repair. Ann N Y Acad Sci. 2009;1176:101–17.CrossRef Bernardo ME, Locatelli F, Fibbe WE. Mesenchymal stromal cells: a novel treatment modality for tissue repair. Ann N Y Acad Sci. 2009;1176:101–17.CrossRef
Metadata
Title
RETRACTED ARTICLE: Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis
Authors
Himanshu Bansal
Kristin Comella
Jerry Leon
Poonam Verma
Diwaker Agrawal
Prasad Koka
Thomas Ichim
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1242-4

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