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Journal of Orthopaedic Surgery and Research

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01-12-2020 | Painful Arc | Research article

Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study

Authors: Jason L. Hurd, Tiffany R. Facile, Jennifer Weiss, Matthew Hayes, Meredith Hayes, John P. Furia, Nicola Maffulli, Glenn E. Winnier, Christopher Alt, Christoph Schmitz, Eckhard U. Alt, Mark Lundeen

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2020

Abstract

Background

This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tears (sPTRCT) with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and more effective than corticosteroid injection.

Methods

Subjects aged between 30 and 75 years with sPTRCT who did not respond to physical therapy treatments for at least 6 weeks were randomly assigned to receive a single injection of an average 11.4 × 10⁶ UA-ADRCs (in 5 mL liquid; mean cell viability: 88%) (n = 11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/mL; 2 mL) plus 3 mL of 0.25% bupivacaine (n = 5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey, and pain visual analogue scale (VAS) at baseline (BL) as well as 3 weeks (W3), W6, W9, W12, W24, W32, W40, and W52 post treatment. Fat-saturated T2-weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment.

Results

No severe adverse events related to the injection of UA-ADRCs were observed in the 12 months post treatment. The risks connected with treatment of sPTRCT with UA-ADRCs were not greater than those connected with treatment of sPTRCT with corticosteroid injection. However, one subject in the corticosteroid group developed a full rotator cuff tear during the course of this pilot study. Despite the small number of subjects in this pilot study, those in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than those in the corticosteroid group (p < 0.05).

Discussion

This pilot study suggests that the use of UA-ADRCs in subjects with sPTRCT is safe and leads to improved shoulder function without adverse effects. To verify the results of this initial safety and feasibility pilot study in a larger patient population, a randomized controlled trial on 246 patients suffering from sPTRCT is currently ongoing.

Trial registration

Clinicaltrials.gov ID NCT02918136. Registered September 28, 2016, https://clinicaltrials.gov/ct2/show/NCT02918136.

Level of evidence

Level I; prospective, randomized, controlled trial.

Matava MJ, Purcell DB, Rudzki JR. Partial-thickness rotator cuff tears. Am J Sports Med. 2005;33(9):1405–17. https://doi.org/10.1177/0363546505280213.CrossRefPubMed

Via AG, De Cupis M, Spoliti M, Oliva F. Clinical and biological aspects of rotator cuff tears. Muscles Ligaments Tendons J. 2013;3(2):70–9. https://doi.org/10.11138/mltj/2013.3.2.070.CrossRefPubMed

Matthewson G, Beach CJ, Nelson AA, Woodmass JM, Ono Y, Boorman RS, Lo IK, Thornton GM. Partial thickness rotator cuff tears: current concepts. Adv Orthop. 2015;2015:458786. https://doi.org/10.1155/2015/458786.CrossRefPubMedPubMedCentral

Ellman H. Diagnosis and treatment of incomplete rotator cuff tears. Clin Orthop Relat Res. 1990;254:64–74.

Cotton RE, Rideout DF. Tears of the humeral rotator cuff. J Bone Joint Surg. 1964;46B(2):314–28.CrossRef

Fukuda H. Partial-thickness rotator cuff tears: a modern view on Codman's classic. J Shoulder Elbow Surg. 2000;9(2):163–8.CrossRef

Sher JS, Uribe JW, Posada A, Murphy BJ, Zlatkin MB. Abnormal findings on magnetic resonance images of asymptomatic shoulders. J Bone Joint Surg Am. 1995;77(1):10–5. https://doi.org/10.2106/00004623-199501000-00002.CrossRefPubMed

Payne LZ, Altchek DW, Craig EV, Warren RF. Arthroscopic treatment of partial rotator cuff tears in young athletes: a preliminary report. Am J Sports Med. 1997;25(3):299–305. https://doi.org/10.1177/036354659702500305.CrossRefPubMed

https://www.aaos.org/research/guidelines/rcp_summary.pdf [cited 10 February 2020].

10.

Checketts JX, Scott J, Gordon J, Jones J, Horn J, Farabough M, Whitener J, Boose M, Vassar M. An evaluation of the rotator cuff repair research pipeline. Orthop J Sports Med. 2018;6(11):2325967118805731. https://doi.org/10.1177/2325967118805731.CrossRefPubMedPubMedCentral

11.

Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet. 2010;376(9754):1751–67. https://doi.org/10.1016/S0140-6736(10)61160-9.CrossRefPubMed

12.

https://clincalc.com/Corticosteroids/ [cited 10 February 2020].

13.

Zhang J, Keenan C, Wang JH. The effects of dexamethasone on human patellar tendon stem cells: implications for dexamethasone treatment of tendon injury. J Orthop Res. 2013;31(1):105–10. https://doi.org/10.1002/jor.22193.CrossRefPubMed

14.

Ramírez J, Pomés I, Cabrera S, Pomés J, Sanmartí R, Cañete JD. Incidence of full-thickness rotator cuff tear after subacromial corticosteroid injection: a 12-week prospective study. Mod Rheumatol. 2014;24(4):667–70. https://doi.org/10.3109/14397595.2013.857798.CrossRefPubMed

15.

Puzzitiello RN, Patel BH, Nwachukwu BU, Allen AA, Forsythe B, Salzler MJ. Adverse impact of corticosteroid injection on rotator cuff tendon health and repair: a systematic review. Arthroscopy. 2019. pii: S0749-8063(19)31198-3 [Epub ahead of print]. doi: https://doi.org/10.1016/j.arthro.2019.12.006.

16.

Kukkonen J, Joukainen A, Lehtinen J, Mattila KT, Tuominen EK, Kauko T, Aärimaa V. Treatment of non-traumatic rotator cuff tears: a randomised controlled trial with one-year clinical results. Bone Joint J. 2014;96-B(1):75–81. https://doi.org/10.1302/0301-620X.96B1.32168.CrossRefPubMed

17.

Kim SJ, Kim SH, Lim SH, Chun YM. Use of magnetic resonance arthrography to compare clinical features and structural integrity after arthroscopic repair of bursal versus articular side partial-thickness rotator cuff tears. Am J Sports Med. 2013;41(9):2041–7. https://doi.org/10.1177/0363546513496214.CrossRefPubMed

18.

Kim KC, Shin HD, Cha SM, Park JY. Repair integrity and functional outcome after arthroscopic conversion to a full-thickness rotator cuff tear: articular- versus bursal-side partial tears. Am J Sports Med. 2014;42(2):451–6. https://doi.org/10.1177/0363546513512770.CrossRefPubMed

19.

Kim SH, Chung SW, Oh JH. Expression of insulin-like growth factor type 1 receptor and myosin heavy chain in rabbit's rotator cuff muscle after injection of adipose-derived stem cell. Knee Surg Sports Traumatol Arthrosc. 2014;22(11):2867–73. https://doi.org/10.1007/s00167-013-2560-6.CrossRefPubMed

20.

Valencia Mora M, Antuña Antuña S, García Arranz M, Carrascal MT, Barco R. Application of adipose tissue-derived stem cells in a rat rotator cuff repair model. Injury. 2014;45(Suppl 4):S22–7. https://doi.org/10.1016/S0020-1383(14)70006-3.CrossRefPubMed

21.

Chen HS, Su YT, Chan TM, Su YJ, Syu WS, Harn HJ, Lin SZ, Chiu SC. Human adipose-derived stem cells accelerate the restoration of tensile strength of tendon and alleviate the progression of rotator cuff injury in a rat model. Cell Transplant. 2015;24(3):509–20. https://doi.org/10.3727/096368915X686968.CrossRefPubMed

22.

Gumucio JP, Flood MD, Roche SM, Sugg KB, Momoh AO, Kosnik PE, Bedi A, Mendias CL. Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear. Int Orthop. 2016;40(4):759–64. https://doi.org/10.1007/s00264-015-2937-x.CrossRefPubMed

23.

Tsekes D, Konstantopoulos G, Khan WS, Rossouw D, Elvey M, Singh J. Use of stem cells and growth factors in rotator cuff tendon repair. Eur J Orthop Surg Traumatol. 2019;29(4):747–57. https://doi.org/10.1007/s00590-019-02366-x.CrossRefPubMed

24.

Andia I, Martin JI, Maffulli N. Platelet-rich plasma and mesenchymal stem cells: exciting, but … are we there yet? Sports Med Arthrosc Rev. 2018;26(2):59–63. https://doi.org/10.1097/JSA.0000000000000191.CrossRefPubMed

25.

Hurley ET, Hannon CP, Pauzenberger L, Fat DL, Moran CJ, Mullett H. Nonoperative treatment of rotator cuff disease with platelet-rich plasma: a systematic review of randomized controlled trials. Arthroscopy. 2019;35(5):1584–91. https://doi.org/10.1016/j.arthro.2018.10.115.CrossRefPubMed

26.

Schwitzguebel AJ, Kolo FC, Tirefort J, Kourhani A, Nowak A, Gremeaux V, Saffarini M, Lädermann A. Efficacy of platelet-rich plasma for the treatment of interstitial supraspinatus tears: a double-blinded, randomized controlled trial. Am J Sports Med. 2019;47(8):1885–92. https://doi.org/10.1177/0363546519851097.CrossRefPubMed

27.

Alt EU, Schmitz C, Bai X. Fundamentals of Stem cells: why and how patients' own adult stem cells are the next generation of medicine. In: Trafny T, Spiri S, editors. Bioethics and research on adult stem cells. Rome: IF Press; 2020. in press.

28.

Winnier GE, Valenzuela N, Peters-Hall J, Kellner J, Alt C, Alt EU. Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent. PLoS One. 2019;14(9):e0221457. https://doi.org/10.1371/journal.pone.0221457.CrossRefPubMedPubMedCentral

29.

Solakoglu Ö, Götz W, Kiessling MC, Alt C, Schmitz C, Alt EU. Improved guided bone regeneration by combined application of unmodified, fresh autologous adipose derived regenerative cells and plasma rich in growth factors: A first-in-human case report and literature review. World J Stem Cells. 2019;11(2):124–46. https://doi.org/10.4252/wjsc.v11.i2.124.CrossRefPubMedPubMedCentral

30.

Haenel A, Ghosn M, Karimi T, Vykoukal J, Shah D, Valderrabano M, Schulz DG, Raizner A, Schmitz C, Alt EU. Unmodified autologous stem cells at point of care for chronic myocardial infarction. World J Stem Cells. 2019;11(10):831–58. https://doi.org/10.4252/wjsc.v11.i10.831.CrossRefPubMedPubMedCentral

31.

Boutron I, Altman DG, Moher D, Schulz KF, Ravaud P, CONSORT NPT Group. CONSORT Statement for randomized trials of nonpharmacologic treatments: a 2017 Update and a CONSORT extension for nonpharmacologic trial abstracts. Ann Intern Med. 2017;167(1):40–7. https://doi.org/10.7326/M17-0046.CrossRefPubMed

32.

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7. https://doi.org/10.7326/0003-4819-158-3-201302050-00583.CrossRefPubMedPubMedCentral

33.

Ben Kibler W, Sciascia AD, Hester P, Dome D, Jacobs C. Clinical utility of traditional and new tests in the diagnosis of biceps tendon injuries and superior labrum anterior and posterior lesions in the shoulder. Am J Sports Med. 2009;37(9):1840–7. https://doi.org/10.1177/0363546509332505.CrossRefPubMed

34.

Neer CS 2nd. Impingement lesions. Clin Orthop Relat Res. 1983;(173):70–7.

35.

European Medicine Agency. Guideline on missing data in confirmatory clinical trials, 2010 [cited 10 February 2020]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500096793.pdf.

36.

Coleman WP 4th, Hendry SL 2nd. Principles of liposuction. Semin Cutan Med Surg. 2006;25:138–44. https://doi.org/10.1016/j.sder.2006.06.006.CrossRefPubMed

37.

Klein JA. Tumescent technique for local anesthesia improves safety in large-volume liposuction. Plast Reconstr Surg. 1993;92:1085–98.CrossRef

38.

Ware J, Donald Sherbourne C. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.CrossRef

39.

Hays RD, Sherbourne CD, Mazel RM. The RAND 36-Item Health Survey 1.0. Health Econ. 1993;2(3):217–27.CrossRef

40.

Angst F, Schwyzer HK, Aeschlimann A, Simmen BR, Goldhahn J. Measures of adult shoulder function: Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) and its short version (QuickDASH), Shoulder Pain and Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) Society standardized shoulder assessment form, Constant (Murley) Score (CS), Simple Shoulder Test (SST), Oxford Shoulder Score (OSS), Shoulder Disability Questionnaire (SDQ), and Western Ontario Shoulder Instability Index (WOSI). Arthritis Care Res. 2011;63 Suppl 11:S174-S188. doi: https://doi.org/10.1002/acr.20630.

41.

Wylie JD, Beckmann JT, Granger E, Tashjian RZ. Functional outcomes assessment in shoulder surgery. World J Orthop. 2014;5(5):623–33. https://doi.org/10.5312/wjo.v5.i5.623.CrossRefPubMedPubMedCentral

42.

Lins L, Carvalho FM. SF-36 total score as a single measure of health-related quality of life: Scoping review. SAGE Open Med. 2016;4:2050312116671725.CrossRef

43.

Bronstein IN, Semendjajew KA. Handbook of Mathematics (3^rd ed). Harri Deutsch, Frankfurt/Main, 1985.

44.

Hurd J. Autologous adult adipose-derived regenerative cell injection into chronic partial-thickness rotator cuff tears. ClinicalTrials.gov Identifier: NCT03752827 [cited 09 December 2019]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03752827.

45.

https://www.meddra.org/ [cited 10 February 2019].

46.

Aronowitz JA, Lockhart RA, Hakakian CS, Birnbaum ZE. Adipose stromal vascular fraction isolation: A head-to-head comparison of 4 cell separation systems #2. Ann Plast Surg. 2016;77(3):354–62. https://doi.org/10.1097/SAP.0000000000000831.CrossRefPubMed

47.

Alt E, Milz S, Frank HG, Rothoerl R, Hoppert M, Alt C, Winnier G, Schmitz C. Rotator cuff tear treated with adipose derived regenerative cells. Submitted for publication.

48.

Bai X, Yan Y, Coleman M, Wu G, Rabinovich B, Seidensticker M, Alt E. Tracking long-term survival of intramyocardially delivered human adipose tissue-derived stem cells using bioluminescence imaging. Mol Imaging Biol. 2011;13(4):633–45. https://doi.org/10.1007/s11307-010-0392-z.CrossRefPubMed

49.

Sadat S, Gehmert S, Song YH, Yen Y, Bai X, Gaiser S, Klein H, Alt E. The cardioprotective effect of mesenchymal stem cells is mediated by IGF-I and VEGF. Biochem Biophys Res Commun. 2007;363(3):674–9. https://doi.org/10.1016/j.bbrc.2007.09.058.CrossRefPubMed

50.

González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology. 2009;136(3):978–89. https://doi.org/10.1053/j.gastro.2008.11.041.CrossRefPubMed

51.

Leto Barone AA, Khalifian S, Lee WP, Brandacher G. Immunomodulatory effects of adipose-derived stem cells: fact or fiction? Biomed Res Int. 2013;2013:383685. https://doi.org/10.1155/2013/383685.CrossRefPubMedPubMedCentral

52.

Ellera Gomes JL, da Silva RC, Silla LMR, Abreu MR, Pellanda R. Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc. 2012;20(2):373–7. https://doi.org/10.1007/s00167-011-1607-9.CrossRefPubMed

53.

Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014;38(9):1811–8. https://doi.org/10.1007/s00264-014-2391-1.CrossRefPubMed

54.

Havlas V, Kotaška J, Koníček P, Trč T, Konrádová Š, Kočí Z, Syková E. Pouziti kultivovanych lidskych autolognich kmenovych bunek kostni drene pri rekonstrukci ruptury rotatorove manzety - studie bezpecnosti metody, predbezne vysledky [Use of cultured human autologous bone marrow stem cells in repair of a rotator cuff tear: preliminary results of a safety study] [Article in Czech]. Acta Chir Orthop Traumatol Cech. 2015;82(3):229–34.PubMed

55.

Kim YS, Sung CH, Chung SH, Kwak SJ, Koh YG. Does an injection of adipose-derived mesenchymal stem cells loaded in fibrin glue influence rotator cuff repair outcomes? a clinical and magnetic resonance imaging study. Am J Sports Med. 2017 Jul;45(9):2010–8. https://doi.org/10.1177/0363546517702863.CrossRefPubMed

56.

Jo CH, Chai JW, Jeong EC, Oh S, Kim PS, Yoon JY, Yoon KS. Intratendinous injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of rotator cuff disease: a first-in-human trial. Stem Cells. 2018;36(9):1441–50. https://doi.org/10.1002/stem.2855.CrossRefPubMed

57.

Cossu G, Birchall M, Brown T, De Coppi P, Culme-Seymour E, Gibbon S, Hitchcock J, Mason C, Montgomery J, Morris S, Muntoni F, Napier D, Owji N, Prasad A, Round J, Saprai P, Stilgoe J, Thrasher A, Wilson J. Lancet Commission: Stem cells and regenerative medicine. Lancet. 2018;391(10123):883–910. https://doi.org/10.1016/S0140-6736(17)31366-1.CrossRefPubMed

58.

Jo CH, Shin JS, Park IW, Kim H, Lee SY. Multiple channeling improves the structural integrity of rotator cuff repair. Am J Sports Med. 2013;41(11):2650–7. https://doi.org/10.1177/0363546513499138.CrossRefPubMed

59.

Taniguchi N, Suenaga N, Oizumi N, Miyoshi N, Yamaguchi H, Inoue K, Chosa E. Bone marrow stimulation at the footprint of arthroscopic surface-holding repair advances cuff repair integrity. J Shoulder Elbow Surg. 2015;24(6):860–6. https://doi.org/10.1016/j.jse.2014.09.031.CrossRefPubMed

60.

Osti L, Del Buono A, Maffulli N. Microfractures at the rotator cuff footprint: a randomised controlled study. Int Orthop. 2011;37(11):2165–71. https://doi.org/10.1007/s00264-013-1952-z.CrossRef

61.

Cai YZ, Zhang C, Lin XJ. Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis. J Shoulder Elbow Surg. 2015;24(12):1852–9. https://doi.org/10.1016/j.jse.2015.07.035.CrossRefPubMed

62.

Warth RJ, Dornan GJ, James EW, Horan MP, Millett PJ. Clinical and structural outcomes after arthroscopic repair of full-thickness rotator cuff tears with and without platelet-rich product supplementation: a meta-analysis and meta-regression. Arthroscopy. 2015;31(2):306–20. https://doi.org/10.1016/j.arthro.2014.09.007.CrossRefPubMed

63.

Fu CJ, Sun JB, Bi ZG, Wang XM, Yang CL. Evaluation of platelet-rich plasma and fibrin matrix to assist in healing and repair of rotator cuff injuries: a systematic review and meta-analysis. Clin Rehabil. 2017;31(2):158–72. https://doi.org/10.1177/0269215516634815.CrossRefPubMed

64.

Miranda I, Sánchez-Alepuz E, Lucas FJ, Carratalá V, González-Jofre CA. Use of platelet-rich plasma in the treatment of rotator cuff pathology. What has been scientifically proven? Rev Esp Cir Ortop Traumatol. 2017;61(4):249–58. https://doi.org/10.1016/j.recot.2017.03.001.CrossRefPubMed

65.

Hurley ET, Lim Fat D, Moran CJ, Mullett H. The efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials. Am J Sports Med. 2019;47(3):753–61. https://doi.org/10.1177/0363546517751397.CrossRefPubMed

66.

Jazrawi LM, Baron SL. Editorial commentary: sprinkle some pixie dust on it-are we really any better at understanding the benefits of platelet-rich plasma for rotator cuff pathology? Arthroscopy. 2019;35(5):1592–3. https://doi.org/10.1016/j.arthro.2019.02.009.CrossRefPubMed

67.

Han C, Na Y, Zhu Y, Kong L, Eerdun T, Yang X, Ren Y. Is platelet-rich plasma an ideal biomaterial for arthroscopic rotator cuff repair? A systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2019;14(1):183. https://doi.org/10.1186/s13018-019-1207-9.CrossRefPubMedPubMedCentral

68.

Murray IR, LaPrade RF, Musahl V, Geeslin AG, Zlotnicki JP, Mann BJ, Petrigliano FA. Biologic treatments for sports injuries II Think tank-current concepts, future research, and barriers to advancement, Part 2: rotator cuff. Orthop J Sports Med. 201631;4(3):2325967116636586. https://doi.org/10.1177/2325967116636586.

69.

Coory JA, Parr AF, Wilkinson MP, Gupta A. Efficacy of suprascapular nerve block compared with subacromial injection: a randomized controlled trial in patients with rotator cuff tears. J Shoulder Elbow Surg. 2019;28(3):430–6. https://doi.org/10.1016/j.jse.2018.11.051.CrossRefPubMed

Title: Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study
Authors: Jason L. Hurd
Tiffany R. Facile
Jennifer Weiss
Matthew Hayes
Meredith Hayes
John P. Furia
Nicola Maffulli
Glenn E. Winnier
Christopher Alt
Christoph Schmitz
Eckhard U. Alt
Mark Lundeen
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Painful Arc
Care
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2020
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-020-01631-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study

Abstract

Background

Methods

Results

Discussion

Trial registration

Level of evidence

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Discussion

Trial registration

Level of evidence

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