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Published in: Arthritis Research & Therapy 1/2023

Open Access 01-12-2023 | Knee Osteoarthritis | Review

Effect of intra-knee injection of autologous adipose stem cells or mesenchymal vascular components on short-term outcomes in patients with knee osteoarthritis: an updated meta-analysis of randomized controlled trials

Authors: Yang Yang, Zhibin Lan, Jiangbo Yan, Zhiqun Tang, Linghui Zhou, Dian Jin, Qunhua Jin

Published in: Arthritis Research & Therapy | Issue 1/2023

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Abstract

Objective

Assess the efficacy of single and multiple intra-articular injections of autologous adipose-derived stem cells (ASCs) and adipose-derived stromal vascular fraction (ADSVF) for the treatment of knee osteoarthritis (OA).

Methods

We conducted a thorough and systematic search of several databases, including PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, to identify relevant studies. The included studies were randomized controlled trials (RCTs) that involved single or multiple intra-articular injections of autologous ASCs or ADSVF for the treatment of patients with knee osteoarthritis, without any additional treatment, and compared to either placebo or hyaluronic acid.

Results

A total of seven RCTs were analyzed in this study. The results of the meta-analysis show that compared to the control group, both single and multiple intra-articular injections of ASCs or ADSVF demonstrated superior pain relief in the short term (Z = 3.10; P < 0.0001 and Z = 4.66; P < 0.00001) and significantly improved function (Z = 2.61; P < 0.009 and Z = 2.80; P = 0.005). Furthermore, MRI assessment showed a significant improvement in cartilage condition compared to the control group. (Z = 8.14; P < 0.000001 and Z = 5.58; P < 0.00001).

Conclusions

In conclusion, in osteoarthritis of the knee, single or multiple intra-articular injections of autologous ASCs or ADSVF have shown significant pain improvement and safety in the short term in the absence of adjuvant therapy. Significant improvements in cartilage status were also shown. A larger sample size of randomized controlled trials is needed for direct comparison of the difference in effect between single and multiple injections.
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Literature
1.
go back to reference Callahan LF, Ambrose KR, Albright AL, Altpeter M, Golightly YM, Huffman KF, et al. Public Health Interventions for Osteoarthritis - updates on the Osteoarthritis Action Alliance’s efforts to address the 2010 OA Public Health Agenda Recommendations. Clin Exp Rheumatol. 2019;5:31–9. Callahan LF, Ambrose KR, Albright AL, Altpeter M, Golightly YM, Huffman KF, et al. Public Health Interventions for Osteoarthritis - updates on the Osteoarthritis Action Alliance’s efforts to address the 2010 OA Public Health Agenda Recommendations. Clin Exp Rheumatol. 2019;5:31–9.
2.
go back to reference Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol. 2019;5:3–6. Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol. 2019;5:3–6.
3.
go back to reference Zhang Y, Zhang JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;3:355–69.CrossRef Zhang Y, Zhang JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;3:355–69.CrossRef
4.
go back to reference Madry H, Kon E, Condello V, Peretti GM, Steinwachs M, Seil R, et al. Early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2016;24:1753–62.CrossRefPubMed Madry H, Kon E, Condello V, Peretti GM, Steinwachs M, Seil R, et al. Early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2016;24:1753–62.CrossRefPubMed
5.
go back to reference Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Sur. 2013;9(559):557. Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Sur. 2013;9(559):557.
6.
go back to reference McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22:363–88.CrossRefPubMed McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22:363–88.CrossRefPubMed
7.
go back to reference Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16:137–62.CrossRefPubMed Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16:137–62.CrossRefPubMed
8.
go back to reference Ha C, Park Y, Kim SH, Lee H. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: a systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy. 2019;35:277–88.CrossRefPubMed Ha C, Park Y, Kim SH, Lee H. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: a systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy. 2019;35:277–88.CrossRefPubMed
9.
go back to reference Mazor M, Lespessailles E, Coursier R, Daniellou R, Best TM, Toumi H. Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med. 2014;18:2340–50.CrossRefPubMedPubMedCentral Mazor M, Lespessailles E, Coursier R, Daniellou R, Best TM, Toumi H. Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med. 2014;18:2340–50.CrossRefPubMedPubMedCentral
10.
go back to reference Pastides P, Chimutengwende-Gordon M, Maffulli N, Khan W. Stem cell therapy for human cartilage defects: a systematic review. Osteoarthritis Cartilage. 2013;21:646–54.CrossRefPubMed Pastides P, Chimutengwende-Gordon M, Maffulli N, Khan W. Stem cell therapy for human cartilage defects: a systematic review. Osteoarthritis Cartilage. 2013;21:646–54.CrossRefPubMed
11.
12.
go back to reference Jeyaraman M, Muthu S, Ganie PA. Does the source of mesenchymal stem cell have an effect in the management of osteoarthritis of the knee? Meta-Analysis of Randomized Controlled Trials Cartilage. 2021;13:1532S-1547S.PubMed Jeyaraman M, Muthu S, Ganie PA. Does the source of mesenchymal stem cell have an effect in the management of osteoarthritis of the knee? Meta-Analysis of Randomized Controlled Trials Cartilage. 2021;13:1532S-1547S.PubMed
13.
go back to reference Shariatzadeh M, Song J, Wilson SL. The efficacy of different sources of mesenchymal stem cells for the treatment of knee osteoarthritis. Cell Tissue Res. 2019;378:399–410.CrossRefPubMed Shariatzadeh M, Song J, Wilson SL. The efficacy of different sources of mesenchymal stem cells for the treatment of knee osteoarthritis. Cell Tissue Res. 2019;378:399–410.CrossRefPubMed
14.
go back to reference Yokota N, Hattori M, Ohtsuru T, Otsuji M, Lyman S, Shimomura K, et al. Comparative clinical outcomes after intra-articular injection with adipose-derived cultured stem cells or noncultured stromal vascular fraction for the treatment of knee osteoarthritis. Am J Sports Med. 2019;47:2577–83.CrossRefPubMed Yokota N, Hattori M, Ohtsuru T, Otsuji M, Lyman S, Shimomura K, et al. Comparative clinical outcomes after intra-articular injection with adipose-derived cultured stem cells or noncultured stromal vascular fraction for the treatment of knee osteoarthritis. Am J Sports Med. 2019;47:2577–83.CrossRefPubMed
15.
go back to reference Usuelli FG, D Ambrosi R, Maccario C, Indino C, Manzi L, Maffulli N. Adipose-derived stem cells in orthopaedic pathologies. Br Med Bull. 2017;124:1–24. Usuelli FG, D Ambrosi R, Maccario C, Indino C, Manzi L, Maffulli N. Adipose-derived stem cells in orthopaedic pathologies. Br Med Bull. 2017;124:1–24.
16.
go back to reference Kim K, Kim M, Kim J. Intra-articular injection of autologous adipose-derived stem cells or stromal vascular fractions: are they effective for patients with knee osteoarthritis? A systematic review with meta-analysis of randomized controlled trials. Am J Sports Med. 2023;51:837–48.CrossRefPubMed Kim K, Kim M, Kim J. Intra-articular injection of autologous adipose-derived stem cells or stromal vascular fractions: are they effective for patients with knee osteoarthritis? A systematic review with meta-analysis of randomized controlled trials. Am J Sports Med. 2023;51:837–48.CrossRefPubMed
17.
go back to reference Lu L, Dai C, Zhang Z, Du H, Li S, Ye P, et al. Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem Cell Res Ther. 2019;10:143. Lu L, Dai C, Zhang Z, Du H, Li S, Ye P, et al. Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem Cell Res Ther. 2019;10:143.
18.
go back to reference Lee, WS, Kim, HJ, Kim, KI, et al. Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem Cells Transl Med. 2019;8:504–11. Lee, WS, Kim, HJ, Kim, KI, et al. Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem Cells Transl Med. 2019;8:504–11.
19.
go back to reference Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.CrossRefPubMedPubMedCentral Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.CrossRefPubMedPubMedCentral
20.
go back to reference Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;7:e1–34. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;7:e1–34.
22.
go back to reference Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;7414:557–60.CrossRef Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;7414:557–60.CrossRef
23.
go back to reference Zhang S, Xu H, He B, Fan M, Xiao M, Zhang J, et al. Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study. Stem Cell Res Ther. 2021;13:105. Zhang S, Xu H, He B, Fan M, Xiao M, Zhang J, et al. Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study. Stem Cell Res Ther. 2021;13:105.
24.
go back to reference Zhang Y, Bi Q, Luo J, Tong Y, Yu T, Zhang Q. The effect of autologous adipose-derived stromal vascular fractions on cartilage regeneration was quantitatively evaluated based on the 3D-FS-SPGR sequence: a clinical trial study. Biomed Res Int. 2021;2022:1–17. Zhang Y, Bi Q, Luo J, Tong Y, Yu T, Zhang Q. The effect of autologous adipose-derived stromal vascular fractions on cartilage regeneration was quantitatively evaluated based on the 3D-FS-SPGR sequence: a clinical trial study. Biomed Res Int. 2021;2022:1–17.
25.
go back to reference Garza JR, Campbell RE, Tjoumakaris FP, Freedman KB, Miller LS, Santa Maria D, et al. Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial. Am J Sports Med. 2020;48:588–98.CrossRefPubMed Garza JR, Campbell RE, Tjoumakaris FP, Freedman KB, Miller LS, Santa Maria D, et al. Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial. Am J Sports Med. 2020;48:588–98.CrossRefPubMed
26.
go back to reference Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14:213–30. Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14:213–30.
27.
go back to reference Hong Z, Chen J, Zhang S, Zhao C, Bi M, Chen X, et al. Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial. Int Orthop. 2019;43:1123–34. Hong Z, Chen J, Zhang S, Zhao C, Bi M, Chen X, et al. Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial. Int Orthop. 2019;43:1123–34.
28.
go back to reference Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15:422.PubMed Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15:422.PubMed
29.
go back to reference Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, et al. Long-term follow-up of intra-articular injection of autologous mesenchymal stem cells in patients with knee, ankle, or hip osteoarthritis. Arch Iran Med. 2015;18:336.PubMed Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, et al. Long-term follow-up of intra-articular injection of autologous mesenchymal stem cells in patients with knee, ankle, or hip osteoarthritis. Arch Iran Med. 2015;18:336.PubMed
30.
go back to reference Hurley ET, Yasui Y, Gianakos AL, Seow D, Shimozono Y, Kerkhoffs GMMJ, et al. Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018;26:3499–507.CrossRefPubMed Hurley ET, Yasui Y, Gianakos AL, Seow D, Shimozono Y, Kerkhoffs GMMJ, et al. Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018;26:3499–507.CrossRefPubMed
31.
go back to reference Ding W, Xu Y, Zhang Y, Li A, Qiu X, Wen H, et al. Efficacy and safety of intra-articular cell-based therapy for osteoarthritis: systematic review and network meta-analysis. CARTILAGE. 2021;13:104S–115S.CrossRefPubMed Ding W, Xu Y, Zhang Y, Li A, Qiu X, Wen H, et al. Efficacy and safety of intra-articular cell-based therapy for osteoarthritis: systematic review and network meta-analysis. CARTILAGE. 2021;13:104S–115S.CrossRefPubMed
32.
go back to reference McIntyre JA, Jones IA, Han B, Vangsness CT. Intra-articular mesenchymal stem cell therapy for the human joint: a systematic review. Am J Sports Med. 2018;46:3550–63.CrossRefPubMed McIntyre JA, Jones IA, Han B, Vangsness CT. Intra-articular mesenchymal stem cell therapy for the human joint: a systematic review. Am J Sports Med. 2018;46:3550–63.CrossRefPubMed
33.
go back to reference Wang J, Zhou L, Zhang Y, Huang L, Shi Q. Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis. Bone Joint Res. 2020;10:719–28.CrossRef Wang J, Zhou L, Zhang Y, Huang L, Shi Q. Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis. Bone Joint Res. 2020;10:719–28.CrossRef
34.
go back to reference Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH. Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med. 2017;51:1125–33.CrossRefPubMed Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH. Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med. 2017;51:1125–33.CrossRefPubMed
Metadata
Title
Effect of intra-knee injection of autologous adipose stem cells or mesenchymal vascular components on short-term outcomes in patients with knee osteoarthritis: an updated meta-analysis of randomized controlled trials
Authors
Yang Yang
Zhibin Lan
Jiangbo Yan
Zhiqun Tang
Linghui Zhou
Dian Jin
Qunhua Jin
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2023
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-023-03134-3

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