Application of Stem Cell Therapy for ACL Graft Regeneration

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2021 Aug 12

PMID 34381504

Citations 3

Authors

Canlong Wang

Yejun Hu

Shichen Zhang

Dengfeng Ruan

Zizhan Huang

Peiwen He

Honglu Cai

Boon Chin Heng

Xiao Chen

Weiliang Shen

Affiliations

Soon will be listed here.

Abstract

Graft regeneration after anterior cruciate ligament (ACL) reconstruction surgery is a complex three-stage process, which usually takes a long duration and often results in fibrous scar tissue formation that exerts a detrimental impact on the patients' prognosis. Hence, as a regeneration technique, stem cell transplantation has attracted increasing attention. Several different stem cell types have been utilized in animal experiments, and almost all of these have shown good capacity in improving tendon-bone regeneration. Various differentiation inducers have been widely applied together with stem cells to enhance specific lineage differentiation, such as recombinant gene transfection, growth factors, and biomaterials. Among the various different types of stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) have been investigated the most, while ligament stem progenitor cells (LDSCs) have demonstrated the best potential in generating tendon/ligament lineage cells. In the clinic, 4 relevant completed trials have been reported, but only one trial with BMSCs showed improved outcomes, while 5 relevant trials are still in progress. This review describes the process of ACL graft regeneration after implantation and summarizes the current application of stem cells from bench to bedside, as well as discusses future perspectives in this field.

Citing Articles

Integrating Modern Technologies into Traditional Anterior Cruciate Ligament Tissue Engineering.

Sopilidis A, Stamatopoulos V, Giannatos V, Taraviras G, Panagopoulos A, Taraviras S Bioengineering (Basel). 2025; 12(1).

PMID: 39851313 PMC: 11762506. DOI: 10.3390/bioengineering12010039.

ACL injury management: a comprehensive review of novel biotherapeutics.

Yu X, Hu J, Li Y, Wen Y, Li B Front Bioeng Biotechnol. 2024; 12:1455225.

PMID: 39650235 PMC: 11620901. DOI: 10.3389/fbioe.2024.1455225.

Comparative effect of skeletal stem cells versus bone marrow mesenchymal stem cells on rotator cuff tendon-bone healing.

Wang L, Guan C, Zhang T, Zhou Y, Liu Y, Hu J J Orthop Translat. 2024; 47:87-96.

PMID: 39007033 PMC: 11245954. DOI: 10.1016/j.jot.2024.05.005.

Advances in Regenerative Sports Medicine Research.

Wang L, Jiang J, Lin H, Zhu T, Cai J, Su W Front Bioeng Biotechnol. 2022; 10:908751.

PMID: 35646865 PMC: 9136559. DOI: 10.3389/fbioe.2022.908751.

References

Feng C, Chan W, Lam Y, Wang X, Chen P, Niu B . Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes. Stem Cell Reports. 2019; 13(4):713-729. PMC: 6829785. DOI: 10.1016/j.stemcr.2019.08.006. View

Nakajima T, Ikeya M . Development of pluripotent stem cell-based human tenocytes. Dev Growth Differ. 2020; 63(1):38-46. DOI: 10.1111/dgd.12702. View

Zhang X, Ma Y, Fu X, Liu Q, Shao Z, Dai L . Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction. Sci Rep. 2016; 6:19073. PMC: 4705474. DOI: 10.1038/srep19073. View

Bi Y, Ehirchiou D, Kilts T, Inkson C, Embree M, Sonoyama W . Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med. 2007; 13(10):1219-27. DOI: 10.1038/nm1630. View

Kern S, Eichler H, Stoeve J, Kluter H, Bieback K . Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24(5):1294-301. DOI: 10.1634/stemcells.2005-0342. View

Yin Z, Chen X, Chen J, Shen W, Hieu Nguyen T, Gao L . The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials. 2009; 31(8):2163-75. DOI: 10.1016/j.biomaterials.2009.11.083. View

Davey M, Hurley E, Withers D, Moran R, Moran C . Anterior Cruciate Ligament Reconstruction with Platelet-Rich Plasma: A Systematic Review of Randomized Control Trials. Arthroscopy. 2020; 36(4):1204-1210. DOI: 10.1016/j.arthro.2019.11.004. View

Keselowsky B, Collard D, Garcia A . Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc Natl Acad Sci U S A. 2005; 102(17):5953-7. PMC: 1087905. DOI: 10.1073/pnas.0407356102. View

Francis-West P, Parish J, Lee K, Archer C . BMP/GDF-signalling interactions during synovial joint development. Cell Tissue Res. 1999; 296(1):111-9. DOI: 10.1007/s004410051272. View

10.

Sozkesen S, Karahan H, Kurtulmus A, Kayali C, Altay T . PRP on Preventıon of Tunnel Enlargement in ACL Reconstructıon. Ortop Traumatol Rehabil. 2019; 20(4):285-291. DOI: 10.5604/01.3001.0012.6462. View

11.

Uysal A, Mizuno H . Tendon regeneration and repair with adipose derived stem cells. Curr Stem Cell Res Ther. 2009; 5(2):161-7. DOI: 10.2174/157488810791268609. View

12.

Mifune Y, Matsumoto T, Ota S, Nishimori M, Usas A, Kopf S . Therapeutic potential of anterior cruciate ligament-derived stem cells for anterior cruciate ligament reconstruction. Cell Transplant. 2012; 21(8):1651-65. DOI: 10.3727/096368912X647234. View

13.

Liu J, Tao X, Chen L, Han W, Zhou Y, Tang K . CTGF positively regulates BMP12 induced tenogenic differentiation of tendon stem cells and signaling. Cell Physiol Biochem. 2015; 35(5):1831-45. DOI: 10.1159/000373994. View

14.

Kanaya A, Deie M, Adachi N, Nishimori M, Yanada S, Ochi M . Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. Arthroscopy. 2007; 23(6):610-7. DOI: 10.1016/j.arthro.2007.01.013. View

15.

Chen B, Zhang J, Nie D, Zhao G, Fu F, Wang J . Characterization of the structure of rabbit anterior cruciate ligament and its stem/progenitor cells. J Cell Biochem. 2018; 120(5):7446-7457. DOI: 10.1002/jcb.28019. View

16.

Ghebes C, Kelder C, Schot T, Renard A, Pakvis D, Fernandes H . Anterior cruciate ligament- and hamstring tendon-derived cells: in vitro differential properties of cells involved in ACL reconstruction. J Tissue Eng Regen Med. 2015; 11(4):1077-1088. DOI: 10.1002/term.2009. View

17.

Chen J, Altman G, Karageorgiou V, Horan R, Collette A, Volloch V . Human bone marrow stromal cell and ligament fibroblast responses on RGD-modified silk fibers. J Biomed Mater Res A. 2003; 67(2):559-70. DOI: 10.1002/jbm.a.10120. View

18.

Carey J, Shea K . AAOS Clinical Practice Guideline: Management of Anterior Cruciate Ligament Injuries: Evidence-Based Guideline. J Am Acad Orthop Surg. 2015; 23(5):e6-8. DOI: 10.5435/JAAOS-D-15-00095. View

19.

Liu S, Li H, Tao H, Sun Y, Chen S, Chen J . A Randomized Clinical Trial to Evaluate Attached Hamstring Anterior Cruciate Ligament Graft Maturity With Magnetic Resonance Imaging. Am J Sports Med. 2018; 46(5):1143-1149. DOI: 10.1177/0363546517752918. View

20.

Eagan M, ZuK P, Zhao K, Bluth B, Brinkmann E, Wu B . The suitability of human adipose-derived stem cells for the engineering of ligament tissue. J Tissue Eng Regen Med. 2011; 6(9):702-9. DOI: 10.1002/term.474. View