Augmentation of Anterior Cruciate Ligament Reconstruction Using Mesenchymal Stem Cells and Collagen Matrix Carrier

NCT05582226 | Unknown

• 1 other identifier: BioACL2.0
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to compare patient outcomes for reconstructive surgery of ACL tears. This study utilizes two randomized groups, one being the control group that receives standard ACL reconstructive surgery, while the other is the test group at will receive an injection of stem cells taken from elsewhere within the body. The main objectives are to determine the usefulness of stem cells as a cost-effective implant in reconstructive surgery and to determine if the stem cells provide more optimized healing outcomes. Participants will:

• Receive ACL reconstructive surgery as normal
• One-half of the participants will receive stem cells at the repair site as the test group
• All participants will have 3, 6, 9, 12, 18, and 24 month followups to chart their recovery progress Thus, the outcomes of the group receiving stem cell injections will be compared directly with the outcomes of the standard ACL reconstructive care group.

Conditions

ACL Tear

Outcome Measures

Primary Outcomes (6)

• Assessing functional movement using Functional Testing Algorithm

  Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery

  3 months post-operative

• Assessing functional movement using Functional Testing Algorithm

  Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery

  6 months post-operative

• Assessing functional movement using Functional Testing Algorithm

  Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery

  9 months post-operative

• Assessing functional movement using Functional Testing Algorithm

  Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery

  12 months post-operative

• Assessing functional movement using Functional Testing Algorithm

  Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery

  18 months post-operative

• Assessing functional movement using Functional Testing Algorithm

  Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery

  24 months post-operative

Study Arms (2)

ACL reconstruction utilizing stump-derived mesenchymal stem cells

EXPERIMENTAL

This is the test group of this study. These participants will receive the augmented ACL reconstruction treatment involving extraction and injection of mesenchymal stem cells. Stem cell tissue will be harvested from each participant using the GraftNet device intraoperatively. During the intra-articular preparation phase of the reconstruction, the stem cell tissue will be applied to the ACL graft using a bovine collagen matrix.

Procedure: ACL reconstruction; Procedure: Mesenchymal stem cell implantation

Standard of care ACL reconstructive surgery

OTHER

This is the control group of this study. These participants will receive standard ACL reconstructive surgery without any augmentations.

Procedure: ACL reconstruction

Interventions

ACL reconstruction PROCEDURE

Orthopedic surgical operation in which a ruptured anterior cruciate ligament is repaired and reattached to the muscle connection points with a "graft", a fashioned ligament that is meant to serve as a replacement for the ruptured muscle tissue.

ACL reconstruction utilizing stump-derived mesenchymal stem cells; Standard of care ACL reconstructive surgery

Mesenchymal stem cell implantation PROCEDURE

Stem cells are to be extracted from tissue at the stump of the ACL attachment point and inserted on the graft in the hopes of improving healing response

ACL reconstruction utilizing stump-derived mesenchymal stem cells

Eligibility Criteria

• Age: 14 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients between the ages of 14 and 50 who are scheduled to have ACL reconstruction by one of the investigating physicians

You may not qualify if:

• Patients requiring ACL and posterior cruciate ligament combined surgery
• Patients with a history of an autoimmune disease, diabetes, a blood/clotting disorder
• History of previous surgery on the injured knee
• Patients outside of the acceptable age range of this study

Sponsors & Collaborators

• Andrews Research & Education Foundation: lead
• Florida: collaborator

Study Sites (1)

Andrews Research and Education Foundation

Gulf Breeze, Florida, 32561, United States

RECRUITING

Related Publications (35)

• Griffin LY, Agel J, Albohm MJ, Arendt EA, Dick RW, Garrett WE, Garrick JG, Hewett TE, Huston L, Ireland ML, Johnson RJ, Kibler WB, Lephart S, Lewis JL, Lindenfeld TN, Mandelbaum BR, Marchak P, Teitz CC, Wojtys EM. Noncontact anterior cruciate ligament injuries: risk factors and prevention strategies. J Am Acad Orthop Surg. 2000 May-Jun;8(3):141-50. doi: 10.5435/00124635-200005000-00001.

  PMID: 10874221 BACKGROUND

• Gianotti SM, Marshall SW, Hume PA, Bunt L. Incidence of anterior cruciate ligament injury and other knee ligament injuries: a national population-based study. J Sci Med Sport. 2009 Nov;12(6):622-7. doi: 10.1016/j.jsams.2008.07.005. Epub 2008 Oct 2.

  PMID: 18835221 BACKGROUND

• Leathers MP, Merz A, Wong J, Scott T, Wang JC, Hame SL. Trends and Demographics in Anterior Cruciate Ligament Reconstruction in the United States. J Knee Surg. 2015 Oct;28(5):390-4. doi: 10.1055/s-0035-1544193. Epub 2015 Jan 30.

  PMID: 25635874 BACKGROUND

• 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 Sep;38(9):1811-8. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7.

  PMID: 24913770 BACKGROUND

• Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015 Apr 28;35(2):e00191. doi: 10.1042/BSR20150025.

  PMID: 25797907 BACKGROUND

• Anz AW, Branch EA, Rodriguez J, Chillemi F, Bruce JR, Murphy MB, Suzuki RK, Andrews JR. Viable Stem Cells Are in the Injury Effusion Fluid and Arthroscopic Byproducts From Knee Cruciate Ligament Surgery: An In Vivo Analysis. Arthroscopy. 2017 Apr;33(4):790-797. doi: 10.1016/j.arthro.2016.09.036. Epub 2016 Dec 30.

  PMID: 28043750 BACKGROUND

• Branch EA, Matuska AM, Plummer HA, Harrison RM, Anz AW. Platelet-Rich Plasma Devices Can Be Used to Isolate Stem Cells From Synovial Fluid at the Point of Care. Arthroscopy. 2021 Mar;37(3):893-900. doi: 10.1016/j.arthro.2020.09.035. Epub 2020 Oct 1.

  PMID: 33010328 BACKGROUND

• Shi Y, Zhang X, Wan Z, Liu X, Chen F, Zhang J, Leng Y. Mesenchymal stem cells against intestinal ischemia-reperfusion injury: a systematic review and meta-analysis of preclinical studies. Stem Cell Res Ther. 2022 May 26;13(1):216. doi: 10.1186/s13287-022-02896-y.

  PMID: 35619154 BACKGROUND

• Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal Stem Cell Migration and Tissue Repair. Cells. 2019 Jul 28;8(8):784. doi: 10.3390/cells8080784.

  PMID: 31357692 BACKGROUND

• Kim MJ, Son MJ, Son MY, Seol B, Kim J, Park J, Kim JH, Kim YH, Park SA, Lee CH, Lee KS, Han YM, Chang JS, Cho YS. Generation of human induced pluripotent stem cells from osteoarthritis patient-derived synovial cells. Arthritis Rheum. 2011 Oct;63(10):3010-21. doi: 10.1002/art.30488.

  PMID: 21953087 BACKGROUND

• Matsumoto T, Ingham SM, Mifune Y, Osawa A, Logar A, Usas A, Kuroda R, Kurosaka M, Fu FH, Huard J. Isolation and characterization of human anterior cruciate ligament-derived vascular stem cells. Stem Cells Dev. 2012 Apr 10;21(6):859-72. doi: 10.1089/scd.2010.0528. Epub 2011 Aug 17.

  PMID: 21732814 BACKGROUND

• Mifune Y, Matsumoto T, Takayama K, Terada S, Sekiya N, Kuroda R, Kurosaka M, Fu FH, Huard J. Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction. Biomaterials. 2013 Jul;34(22):5476-87. doi: 10.1016/j.biomaterials.2013.04.013. Epub 2013 Apr 28.

  PMID: 23632324 BACKGROUND

• Suzuki S, Muneta T, Tsuji K, Ichinose S, Makino H, Umezawa A, Sekiya I. Properties and usefulness of aggregates of synovial mesenchymal stem cells as a source for cartilage regeneration. Arthritis Res Ther. 2012 Jun 7;14(3):R136. doi: 10.1186/ar3869.

  PMID: 22676383 BACKGROUND

• Horie M, Driscoll MD, Sampson HW, Sekiya I, Caroom CT, Prockop DJ, Thomas DB. Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model. J Bone Joint Surg Am. 2012 Apr 18;94(8):701-12. doi: 10.2106/JBJS.K.00176.

  PMID: 22517386 BACKGROUND

• Koyama N, Okubo Y, Nakao K, Osawa K, Fujimura K, Bessho K. Pluripotency of mesenchymal cells derived from synovial fluid in patients with temporomandibular joint disorder. Life Sci. 2011 Nov 7;89(19-20):741-7. doi: 10.1016/j.lfs.2011.09.005. Epub 2011 Sep 19.

  PMID: 21958469 BACKGROUND

• Harvanova D, Tothova T, Sarissky M, Amrichova J, Rosocha J. Isolation and characterization of synovial mesenchymal stem cells. Folia Biol (Praha). 2011;57(3):119-24. doi: 10.14712/fb2011057030119.

  PMID: 21888835 BACKGROUND

• Sekiya I, Muneta T, Horie M, Koga H. Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects. Clin Orthop Relat Res. 2015 Jul;473(7):2316-26. doi: 10.1007/s11999-015-4324-8. Epub 2015 Apr 30.

  PMID: 25925939 BACKGROUND

• Zhu H, Jiang XX, Wu Y, Liu YL, Li XS, Zhang Y, Mao N. [Identification of mesenchymal stem cells derived from rheumatoid arthritis synovial fluid and their regulatory effect on osteoblast formation]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Aug;17(4):977-80. Chinese.

  PMID: 19698242 BACKGROUND

• Sekiya I, Ojima M, Suzuki S, Yamaga M, Horie M, Koga H, Tsuji K, Miyaguchi K, Ogishima S, Tanaka H, Muneta T. Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis. J Orthop Res. 2012 Jun;30(6):943-9. doi: 10.1002/jor.22029. Epub 2011 Dec 6.

  PMID: 22147634 BACKGROUND

• Matsumoto T, Kubo S, Sasaki K, Kawakami Y, Oka S, Sasaki H, Takayama K, Tei K, Matsushita T, Mifune Y, Kurosaka M, Kuroda R. Acceleration of tendon-bone healing of anterior cruciate ligament graft using autologous ruptured tissue. Am J Sports Med. 2012 Jun;40(6):1296-302. doi: 10.1177/0363546512439026. Epub 2012 Mar 16.

  PMID: 22427618 BACKGROUND

• Radice F, Yanez R, Gutierrez V, Rosales J, Pinedo M, Coda S. Comparison of magnetic resonance imaging findings in anterior cruciate ligament grafts with and without autologous platelet-derived growth factors. Arthroscopy. 2010 Jan;26(1):50-7. doi: 10.1016/j.arthro.2009.06.030.

  PMID: 20117627 BACKGROUND

• Berdis AS, Veale K, Fleissner PR Jr. Outcomes of Anterior Cruciate Ligament Reconstruction Using Biologic Augmentation in Patients 21 Years of Age and Younger. Arthroscopy. 2019 Nov;35(11):3107-3113. doi: 10.1016/j.arthro.2019.05.047. Epub 2019 Aug 19.

  PMID: 31439458 BACKGROUND

• Looney AM, Leider JD, Horn AR, Bodendorfer BM. Bioaugmentation in the surgical treatment of anterior cruciate ligament injuries: A review of current concepts and emerging techniques. SAGE Open Med. 2020 May 12;8:2050312120921057. doi: 10.1177/2050312120921057. eCollection 2020.

  PMID: 32435488 BACKGROUND

• Wang C, Hu Y, Zhang S, Ruan D, Huang Z, He P, Cai H, Heng BC, Chen X, Shen W. Application of Stem Cell Therapy for ACL Graft Regeneration. Stem Cells Int. 2021 Aug 2;2021:6641818. doi: 10.1155/2021/6641818. eCollection 2021.

  PMID: 34381504 BACKGROUND

• Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, Huo H, Loh YH, Aryee MJ, Lensch MW, Li H, Collins JJ, Feinberg AP, Daley GQ. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol. 2011 Nov 27;29(12):1117-9. doi: 10.1038/nbt.2052.

  PMID: 22119740 BACKGROUND

• Musial-Wysocka A, Kot M, Majka M. The Pros and Cons of Mesenchymal Stem Cell-Based Therapies. Cell Transplant. 2019 Jul;28(7):801-812. doi: 10.1177/0963689719837897. Epub 2019 Apr 24.

  PMID: 31018669 BACKGROUND

• Takeuchi H, Niki Y, Matsunari H, Umeyama K, Nagashima H, Enomoto H, Toyama Y, Matsumoto M, Nakamura M. Temporal Changes in Cellular Repopulation and Collagen Fibril Remodeling and Regeneration After Allograft Anterior Cruciate Ligament Reconstruction: An Experimental Study Using Kusabira-Orange Transgenic Pigs. Am J Sports Med. 2016 Sep;44(9):2375-83. doi: 10.1177/0363546516650881. Epub 2016 Jun 21.

  PMID: 27329998 BACKGROUND

• Davies GJ, McCarty E, Provencher M, Manske RC. ACL Return to Sport Guidelines and Criteria. Curr Rev Musculoskelet Med. 2017 Sep;10(3):307-314. doi: 10.1007/s12178-017-9420-9.

  PMID: 28702921 BACKGROUND

• Grassi A, Bailey JR, Signorelli C, Carbone G, Tchonang Wakam A, Lucidi GA, Zaffagnini S. Magnetic resonance imaging after anterior cruciate ligament reconstruction: A practical guide. World J Orthop. 2016 Oct 18;7(10):638-649. doi: 10.5312/wjo.v7.i10.638. eCollection 2016 Oct 18.

  PMID: 27795945 BACKGROUND

• Lundberg M, Styf J, Jansson B. On what patients does the Tampa Scale for Kinesiophobia fit? Physiother Theory Pract. 2009 Oct;25(7):495-506. doi: 10.3109/09593980802662160.

  PMID: 19925172 BACKGROUND

• Brodke DJ, Saltzman CL, Brodke DS. PROMIS for Orthopaedic Outcomes Measurement. J Am Acad Orthop Surg. 2016 Nov;24(11):744-749. doi: 10.5435/JAAOS-D-15-00404.

  PMID: 27661391 BACKGROUND

• O'Connor CM, Ring D. Correlation of Single Assessment Numeric Evaluation (SANE) with other Patient Reported Outcome Measures (PROMs). Arch Bone Jt Surg. 2019 Jul;7(4):303-306.

  PMID: 31448305 BACKGROUND

• Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 2010 Aug 15;12:87-117. doi: 10.1146/annurev-bioeng-070909-105309.

  PMID: 20415588 BACKGROUND

• Yoshihara M, Hayashizaki Y, Murakawa Y. Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications. Stem Cell Rev Rep. 2017 Feb;13(1):7-16. doi: 10.1007/s12015-016-9680-6.

  PMID: 27592701 BACKGROUND

• Takayama K, Kawakami Y, Mifune Y, Matsumoto T, Tang Y, Cummins JH, Greco N, Kuroda R, Kurosaka M, Wang B, Fu FH, Huard J. The effect of blocking angiogenesis on anterior cruciate ligament healing following stem cell transplantation. Biomaterials. 2015 Aug;60:9-19. doi: 10.1016/j.biomaterials.2015.03.036. Epub 2015 May 14.

  PMID: 25965282 BACKGROUND

MeSH Terms

Conditions

Anterior Cruciate Ligament Injuries

Condition Hierarchy (Ancestors)

Knee Injuries; Leg Injuries; Wounds and Injuries

Study Officials

• Adam Anz, MD

  Orthopedic Surgeon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessi Truett, MA, BCBA

CONTACT

8509168570; jessica.truett@andrewsref.org

Matt Farmer, BS

CONTACT

8509168487; matt.farmer@andrewsref.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized into one of two groups, the first group receiving stump stem cell infusion and the second group receiving standard of care ACL reconstruction

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 17, 2022
• Study Start: August 16, 2022
• Primary Completion: August 16, 2023
• Study Completion: August 16, 2023
• Last Updated: February 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)