Skip to main content
Top
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 11/2018

01-11-2018 | Knee

Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis

Authors: Ricardo Bastos, Marcelo Mathias, Renato Andrade, Raquel Bastos, Alex Balduino, Vinicius Schott, Scott Rodeo, João Espregueira-Mendes

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 11/2018

Login to get access

Abstract

Purpose

To compare the effectiveness and safety of intra-articular injections of autologous expanded mesenchymal stromal stem cells alone (MSCs), or in combination with platelet-rich plasma (MSCs + PRP), in patients with knee osteoarthritis.

Methods

Eighteen patients (57.6 ± 9.6 years) with radiographic symptomatic knee osteoarthritis (Dejour grades II–IV) were randomized to receive intra-articular injections of MSCs (n = 9) or MSCs + PRP (n = 9). Injections were performed 2–3 weeks after bone marrow aspiration (± 80–100 ml) which was obtained from both posterior iliac crests.

Results

The Knee Injury and Osteoarthritis Outcome Score (KOOS) improved significantly throughout the 12 months for both groups (p < 0.05). No statistically significant differences between groups were found in KOOS subscales and global score improvements at 12-month end-point (n.s.). The MSCs group showed significant improvements in the pain, function and daily living activities, and sports and recreational activities subscales (p < 0.05). Similarly, the MSCs + PRP group showed significant improvements in the pain, function and daily living activities and quality of life subscales (p < 0.05). The average number of fibroblast colony forming units (CFU-F) was 56.8 + 21.9 for MSCs group and 50.7 ± 21.7 for MSCs + PRP group. Minimal adverse effects were seen in both groups (10 adverse events, in 5 patients).

Conclusions

Intra-articular injections of expanded MSCs alone or in combination with PRP are safe and have a beneficial effect on symptoms in patients with symptomatic knee osteoarthritis. Adding PRP to the MSCs injections did not provide additional benefit. These results are encouraging and support the recommendation of this minimally invasive procedure in patients with knee osteoarthritis, without requiring hospitalization. The CFU-F results may be used as reference for future research.

Level of evidence

Prospective cohort study, Level II.
Appendix
Available only for authorised users
Literature
1.
go back to reference Amable PR, Carias RBV, Teixeira MVT, da Cruz Pacheco Í, do Amaral RJFC., Granjeiro JM et al (2013) Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther 4:67CrossRef Amable PR, Carias RBV, Teixeira MVT, da Cruz Pacheco Í, do Amaral RJFC., Granjeiro JM et al (2013) Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther 4:67CrossRef
2.
go back to reference Bastos Filho R, Magnussen RA, Duthon V, Demey G, Servien E, Granjeiro JM et al (2013) Total knee arthroplasty after high tibial osteotomy: a comparison of opening and closing wedge osteotomy. Int Orthop 37:427–431CrossRef Bastos Filho R, Magnussen RA, Duthon V, Demey G, Servien E, Granjeiro JM et al (2013) Total knee arthroplasty after high tibial osteotomy: a comparison of opening and closing wedge osteotomy. Int Orthop 37:427–431CrossRef
3.
go back to reference Buckwalter JA, Saltzman C, Brown T (2004) The impact of osteoarthritis: implications for research. Clin Orthop Relat Res 427:S6-S15 Buckwalter JA, Saltzman C, Brown T (2004) The impact of osteoarthritis: implications for research. Clin Orthop Relat Res 427:S6-S15
4.
go back to reference Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR et al (2015) Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy 31:2213–2221CrossRef Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR et al (2015) Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy 31:2213–2221CrossRef
5.
go back to reference Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347CrossRef Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347CrossRef
7.
go back to reference Carstairs A, Genever P (2014) Stem cell treatment for musculoskeletal disease. Curr Opin Pharmacol 16:1–6CrossRef Carstairs A, Genever P (2014) Stem cell treatment for musculoskeletal disease. Curr Opin Pharmacol 16:1–6CrossRef
8.
go back to reference da Silva Meirelles L, Sand TT, Harman RJ, Lennon DP, Caplan AI (2008) MSC frequency correlates with blood vessel density in equine adipose tissue. Tissue Eng Part A 15:221–229CrossRef da Silva Meirelles L, Sand TT, Harman RJ, Lennon DP, Caplan AI (2008) MSC frequency correlates with blood vessel density in equine adipose tissue. Tissue Eng Part A 15:221–229CrossRef
9.
go back to reference Dejour H, Carret J, Walch G (1991) Les Gonarthroses. 7émes Journées Lyonnaises de Chirurgie de Genou. 7émes Journées Lyonnaises de Chirurgie de Genou, Les Gonarthroses Dejour H, Carret J, Walch G (1991) Les Gonarthroses. 7émes Journées Lyonnaises de Chirurgie de Genou. 7émes Journées Lyonnaises de Chirurgie de Genou, Les Gonarthroses
11.
go back to reference Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA (2009) Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 37:2259–2272CrossRef Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA (2009) Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 37:2259–2272CrossRef
12.
go back to reference Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L et al (2016) Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy—a review. BMC Musculoskelet Disord 17:230CrossRef Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L et al (2016) Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy—a review. BMC Musculoskelet Disord 17:230CrossRef
13.
go back to reference Gomoll A, Filardo G, De Girolamo L, Esprequeira-Mendes J, Marcacci M, Rodkey W et al (2012) Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc 20:450–466CrossRef Gomoll A, Filardo G, De Girolamo L, Esprequeira-Mendes J, Marcacci M, Rodkey W et al (2012) Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc 20:450–466CrossRef
14.
go back to reference Goncalves R, Cabri J, Pinheiro J, Ferreira P, Gil J (2010) Reliability, validity and responsiveness of the Portuguese version of the Knee injury and Osteoarthritis Outcome Score—Physical Function Short-form (KOOS-PS). Osteoarthritis Cartilage 18:372–376CrossRef Goncalves R, Cabri J, Pinheiro J, Ferreira P, Gil J (2010) Reliability, validity and responsiveness of the Portuguese version of the Knee injury and Osteoarthritis Outcome Score—Physical Function Short-form (KOOS-PS). Osteoarthritis Cartilage 18:372–376CrossRef
15.
go back to reference Goyal D, Keyhani S, Lee EH, Hui JHP (2013) Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy 29:1579–1588CrossRef Goyal D, Keyhani S, Lee EH, Hui JHP (2013) Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy 29:1579–1588CrossRef
16.
go back to reference Haas DA, Kaplan RS (2017) Variation in the cost of care for primary total knee arthroplasties. Arthroplast Today 3:33–37CrossRef Haas DA, Kaplan RS (2017) Variation in the cost of care for primary total knee arthroplasties. Arthroplast Today 3:33–37CrossRef
17.
go back to reference Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J et al (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20:423–435CrossRef Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J et al (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20:423–435CrossRef
18.
go back to reference Ishiguro N, Kojima T, Poole AR (2002) Mechanism of cartilage destruction in osteoarthritis. Nagoya J Med Sci 65:73–84PubMed Ishiguro N, Kojima T, Poole AR (2002) Mechanism of cartilage destruction in osteoarthritis. Nagoya J Med Sci 65:73–84PubMed
19.
go back to reference Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC 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 32:1254–1266CrossRef Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC 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 32:1254–1266CrossRef
20.
go back to reference Khoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D et al (2013) The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy 29:2037–2048CrossRef Khoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D et al (2013) The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy 29:2037–2048CrossRef
21.
go back to reference Koh Y-G, Choi Y-J (2012) Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 19:902–907CrossRef Koh Y-G, Choi Y-J (2012) Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 19:902–907CrossRef
22.
go back to reference Koh Y-G, Jo S-B, Kwon O-R, Suh D-S, Lee S-W, Park S-H et al (2013) Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 29:748–755CrossRef Koh Y-G, Jo S-B, Kwon O-R, Suh D-S, Lee S-W, Park S-H et al (2013) Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 29:748–755CrossRef
23.
go back to reference Koh Y-G, Kwon O-R, Kim Y-S, Choi Y-J (2014) Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy 30:1453–1460CrossRef Koh Y-G, Kwon O-R, Kim Y-S, Choi Y-J (2014) Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy 30:1453–1460CrossRef
24.
go back to reference Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum 58:26–35CrossRef Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum 58:26–35CrossRef
25.
go back to reference Lohmander LS, Roos EM (2007) Clinical update: treating osteoarthritis. Lancet 370:2082–2084CrossRef Lohmander LS, Roos EM (2007) Clinical update: treating osteoarthritis. Lancet 370:2082–2084CrossRef
26.
go back to reference Mazor M, Lespessailles E, Coursier R, Daniellou R, Best T, Toumi H (2014) Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med 18:2340–2350CrossRef Mazor M, Lespessailles E, Coursier R, Daniellou R, Best T, Toumi H (2014) Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med 18:2340–2350CrossRef
27.
go back to reference Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD (2016) Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy 32:495–505CrossRef Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD (2016) Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy 32:495–505CrossRef
28.
go back to reference Mifune Y, Matsumoto T, Takayama K, Ota S, Li H, Meszaros LB et al (2013) The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthritis Cartilage 21:175–185CrossRef Mifune Y, Matsumoto T, Takayama K, Ota S, Li H, Meszaros LB et al (2013) The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthritis Cartilage 21:175–185CrossRef
29.
go back to reference Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V et al (2009) Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng Part C Methods 15:431–435CrossRef Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V et al (2009) Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng Part C Methods 15:431–435CrossRef
30.
go back to reference Osborne H, Anderson L, Burt P, Young M, Gerrard D (2015) Australasian College of Sports Physicians—position statement: the place of mesenchymal stem/stromal cell therapies in sport and exercise medicine. Br J Sports Med 50:1237–1244CrossRef Osborne H, Anderson L, Burt P, Young M, Gerrard D (2015) Australasian College of Sports Physicians—position statement: the place of mesenchymal stem/stromal cell therapies in sport and exercise medicine. Br J Sports Med 50:1237–1244CrossRef
31.
go back to reference Owen M, Friedenstein A (1988) Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 136:42–60PubMed Owen M, Friedenstein A (1988) Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 136:42–60PubMed
32.
go back to reference Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH (2017) Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med 51:1125–1133CrossRef Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH (2017) Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med 51:1125–1133CrossRef
33.
go back to reference Peeters C, Leijs MJ, Reijman M, van Osch G, Bos P (2013) Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage 21:1465–1473CrossRef Peeters C, Leijs MJ, Reijman M, van Osch G, Bos P (2013) Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage 21:1465–1473CrossRef
34.
go back to reference Pers Y-M, Ruiz M, Noël D, Jorgensen C (2015) Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives. Osteoarthritis Cartilage 23:2027–2035CrossRef Pers Y-M, Ruiz M, Noël D, Jorgensen C (2015) Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives. Osteoarthritis Cartilage 23:2027–2035CrossRef
35.
go back to reference Rubio-Azpeitia E, Andia I (2014) Partnership between platelet-rich plasma and mesenchymal stem cells: in vitro experience. Musc Ligaments Tendons J 4:52–62 Rubio-Azpeitia E, Andia I (2014) Partnership between platelet-rich plasma and mesenchymal stem cells: in vitro experience. Musc Ligaments Tendons J 4:52–62
36.
go back to reference Saw K-Y, Anz A, Jee CS-Y, Merican S, Ng RC-S, Roohi SA et al (2013) Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy 29:684–694CrossRef Saw K-Y, Anz A, Jee CS-Y, Merican S, Ng RC-S, Roohi SA et al (2013) Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy 29:684–694CrossRef
37.
go back to reference Tan Y, Jiang M, Yu H, Li J, Qing Z (2013) Therapeutic effect of arthroscopy combined with autologous bone marrow stem cell grafting on knee osteoarthritis. J Tradit Chin Orthop Traumatol 10:35–38 Tan Y, Jiang M, Yu H, Li J, Qing Z (2013) Therapeutic effect of arthroscopy combined with autologous bone marrow stem cell grafting on knee osteoarthritis. J Tradit Chin Orthop Traumatol 10:35–38
38.
go back to reference Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A et al (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99:1681–1690CrossRef Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A et al (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99:1681–1690CrossRef
39.
go back to reference Vinatier C, Mrugala D, Jorgensen C, Guicheux J, Noël D (2009) Cartilage engineering: a crucial combination of cells, biomaterials and biofactors. Trends Biotechnol 27:307–314CrossRef Vinatier C, Mrugala D, Jorgensen C, Guicheux J, Noël D (2009) Cartilage engineering: a crucial combination of cells, biomaterials and biofactors. Trends Biotechnol 27:307–314CrossRef
40.
go back to reference Wolfstadt JI, Cole BJ, Ogilvie-Harris DJ, Viswanathan S, Chahal J (2015) Current concepts: the role of mesenchymal stem cells in the management of knee osteoarthritis. Sports Health 7:38–44CrossRef Wolfstadt JI, Cole BJ, Ogilvie-Harris DJ, Viswanathan S, Chahal J (2015) Current concepts: the role of mesenchymal stem cells in the management of knee osteoarthritis. Sports Health 7:38–44CrossRef
41.
go back to reference Wong KL, Lee KBL, Tai BC, Law P, Lee EH, Hui JH (2013) Injectable cultured bone marrow—derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy 29:2020–2028CrossRef Wong KL, Lee KBL, Tai BC, Law P, Lee EH, Hui JH (2013) Injectable cultured bone marrow—derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy 29:2020–2028CrossRef
42.
go back to reference Xia P, Wang X, Lin Q, Li X (2015) Efficacy of mesenchymal stem cells injection for the management of knee osteoarthritis: a systematic review and meta-analysis. Int Orthop 39:2363–2372CrossRef Xia P, Wang X, Lin Q, Li X (2015) Efficacy of mesenchymal stem cells injection for the management of knee osteoarthritis: a systematic review and meta-analysis. Int Orthop 39:2363–2372CrossRef
43.
go back to reference Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W et al (2012) Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 33:7008–7018CrossRef Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W et al (2012) Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 33:7008–7018CrossRef
44.
go back to reference Zhang W, Moskowitz R, Nuki G, Abramson S, Altman R, Arden N et al (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 16:137–162CrossRef Zhang W, Moskowitz R, Nuki G, Abramson S, Altman R, Arden N et al (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 16:137–162CrossRef
Metadata
Title
Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis
Authors
Ricardo Bastos
Marcelo Mathias
Renato Andrade
Raquel Bastos
Alex Balduino
Vinicius Schott
Scott Rodeo
João Espregueira-Mendes
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 11/2018
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-018-4883-9

Other articles of this Issue 11/2018

Knee Surgery, Sports Traumatology, Arthroscopy 11/2018 Go to the issue