Comparison of ligamentization potential between anterior cruciate ligament-derived cells and adipose-derived mesenchymal stem cells reseeded to acellularized tendon allograft
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Aims: To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods: Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10 6 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results: In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion: ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786.
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An unidentified paracrine action between transplanted ACL-derived cells and the host cells may have enhanced ligament-specific ECM synthesis.
“Besides ligamentous differentiation of ACL-derived cells, an unidentified paracrine action between transplanted ACL-derived cells and the host cells may have enhanced ligament-specific ECM synthesis [22, 62].”
From A new biological enhancement therapy for anterior cruciate ligament reconstruction: the preclinical proof of anterior cruciate ligament reconstruction with tendon graft reseeded with autologous anterior cruciate ligament-derived cells (2025) · cites this paper as [22]
The Key messages and Discussion report greater type I collagen production and higher type I and III collagen gene expression in grafts reseeded with ACL-derived cells. But the study tested acellularized grafts in vitro; it does not establish a paracrine action between transplanted cells and host cells as the reason for that increase. (LLM, conf=0.86)
Experimental — accuracy not yet measuredReseeding culture-expanded anterior cruciate ligament-derived cells to a decellularized tendon graft resulted in a higher gene expression level of type I collagen compared with mesenchymal stem cells derived from adipose tissue.
“In a recent in vitro study, we demonstrated that reseeding culture-expanded ACL-derived cells to a decellularized tendon graft enhanced the graft’s ability to survive and integrate into the tendon’s extracellular matrix (ECM), resulting in a higher gene expression level of type I collagen compared with mesenchymal stem cells derived from adipose tissue, which may lead to the normal ligamentization”
Reseeding culture-expanded anterior cruciate ligament-derived cells to a decellularized tendon graft enhanced the graft's ability to survive and integrate into the tendon's extracellular matrix.
“In a recent in vitro study, we demonstrated that reseeding culture-expanded ACL-derived cells to a decellularized tendon graft enhanced the graft’s ability to survive and integrate into the tendon’s extracellular matrix (ECM), resulting in a higher gene expression level of type I collagen compared with mesenchymal stem cells derived from adipose tissue, which may lead to the normal ligamentization”
Cultured-expanded ACL-derived cells within the tendon microenvironment achieved earlier and superior survival and integration rates in the tendon ECM, resulting in higher type I collagen gene expression compared with adipose-derived MSCs.
“They also demonstrated that cultured-expanded ACL-derived cells within the tendon microenvironment achieved earlier and superior survival and integration rates in the tendon ECM, resulting in higher type I collagen gene expression compared with adipose-derived MSCs [22].”
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Cites
Stöckl, S., Göttl, C., Grifka, J. K., & Grässel, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350089 · Cited by 4,670 · see citing works
Adipose-derived stem cells: Isolation, expansion and differentiation☆
Bunnell, B. A., Flaat, M., Gagliardi, C., PATEL, B., & RIPOLL, C. (2008) · Methods · doi:10.1016/j.ymeth.2008.03.006 · Cited by 1,069 · see citing works
Therapeutic Strategies for Tendon Healing Based on Novel Biomaterials, Factors and Cells
Groß, G., & Hoffmann, A. (2013) · Pathobiology · doi:10.1159/000347059 · Cited by 469 · see citing works
Isolation of adipose-derived stem cells and their induction to a chondrogenic phenotype
Estes, B. T., Diekman, B. O., Gimble, J. M., & Guilak, F. (2010) · Nature Protocols · doi:10.1038/nprot.2010.81 · Cited by 429 · see citing works
Histological Changes in the Human Anterior Cruciate Ligament After Rupture*
MURRAY, M. M., MARTIN, S. D., MARTIN, T. L., & SPECTOR, M. (2000) · The Journal of Bone and Joint Surgery-American Volume · doi:10.2106/00004623-200010000-00004 · Cited by 398 · see citing works
Maffulli, N., Ewen, S. W. B., Waterston, S. W., Reaper, J., & Barrass, V. (2000) · The American Journal of Sports Medicine · doi:10.1177/03635465000280040901 · Cited by 374 · see citing works
Graft remodeling and ligamentization after cruciate ligament reconstruction
Scheffler, S. U., Unterhauser, F. N., & Weiler, A. (2008) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-008-0560-8 · Cited by 266 · see citing works
Harris, M. T., Butler, D. L., Boivin, G. P., Florer, J. B., Schantz, E. J., & WENSTRUP, R. J. (2004) · Journal of Orthopaedic Research® · doi:10.1016/j.orthres.2004.02.012 · Cited by 244 · see citing works
Sánchez, M., Anitua, E., Azofra, J., Prado, R., Muruzabal, F., & Andia, I. (2010) · Arthroscopy · doi:10.1016/j.arthro.2009.08.019 · Cited by 235 · see citing works
“Biological failure” of the anterior cruciate ligament graft
Ménétrey, J., Duthon, V. B., Laumonier, T., & Fritschy, D. (2008) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-007-0474-x · Cited by 227 · see citing works
Allograft Transplantation in the Knee: Tissue Regulation, Procurement, Processing, and Sterilization
Vangsness, C. T., García, I. A., Mills, C. R., Kainer, M. A., Roberts, M. R., & Moore, T. M. (2003) · The American Journal of Sports Medicine · doi:10.1177/03635465030310032701 · Cited by 226 · see citing works
Janssen, R. P. A., & Scheffler, S. U. (2014) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-013-2634-5 · Cited by 225 · see citing works
Tissue Engineering for Anterior Cruciate Ligament Reconstruction: A Review of Current Strategies
Petrigliano, F. A., McAllister, D. R., & Wu, B. M. (2006) · Arthroscopy The Journal of Arthroscopic and Related Surgery · doi:10.1016/j.arthro.2006.01.017 · Cited by 219 · see citing works
Revascularization and ligamentization of autogenous anterior cruciate ligament grafts in humans
Falconiero, R., DiStefano, V., & Cook, T. (1998) · Arthroscopy · doi:10.1016/s0749-8063(98)70041-6 · Cited by 219 · see citing works
Tendon matrix composition and turnover in relation to functional requirements
Birch, H. L. (2007) · International Journal of Experimental Pathology · doi:10.1111/j.1365-2613.2007.00552.x · Cited by 219 · see citing works
IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis
Jo, S., Wang, S. E., Lee, Y. L., Kang, S., Lee, B., Han, J., Sung, I., Park, Y., Bae, S., & Kim, T. (2018) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1582-3 · Cited by 175 · see citing works
Self-citationA Comparison of Tenocytes and Mesenchymal Stem Cells for Use in Flexor Tendon Tissue Engineering
Kryger, G. S., Chong, A. K. S., Costa, M. A., Pham, H. M., Bates, S. R., & Chang, J. (2007) · The Journal Of Hand Surgery · doi:10.1016/j.jhsa.2007.02.018 · Cited by 172 · see citing works
Biodegradable polymer nanocomposites for ligament/tendon tissue engineering
Silva, M. D. S. S. M., Ferreira, F., Alves, N. M., & Paiva, M. C. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-019-0556-1 · Cited by 163 · see citing works
Current Trends in Anterior Cruciate Ligament Reconstruction
Duquin, T. R., Wind, W. M., Fineberg, M. S., Smolinski, R. J., & Buyea, C. M. (2009) · The Journal of Knee Surgery · doi:10.1055/s-0030-1247719 · Cited by 156 · see citing works
Weiler, A., Förster, C., Hunt, P., Falk, R., Jung, T., Unterhauser, F. N., Bergmann, V., Schmidmaier, G., & Haas, N. P. (2004) · The American Journal of Sports Medicine · doi:10.1177/0363546503261711 · Cited by 131 · see citing works
Petersen, W. J., & Laprell, H. (2000) · Knee Surgery Sports Traumatology Arthroscopy · doi:10.1007/s001670050006 · Cited by 124 · see citing works
Pridgen, B. C., Woon, C. Y.-L., Kim, M. Y., Thorfinn, J., Lindsey, D. P., Pham, H. M., & Chang, J. (2011) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2010.0457 · Cited by 116 · see citing works
Ingram, J. H., Korossis, S., Howling, G. I., Fisher, J., & Ingham, E. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0362 · Cited by 111 · see citing works
Remodelling of human hamstring autografts after anterior cruciate ligament reconstruction
Janssen, R. P. A., van der Wijk, J., Fiedler, A., Schmidt, T., Sala, H. A. G. M., & Scheffler, S. U. (2011) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-011-1419-y · Cited by 109 · see citing works
Mifune, Y., Matsumoto, T., Ota, S., Nishimori, M., Usas, A., Kopf, S., Kuroda, R., Kurosaka, M., Fu, F. H., & Huard, J. (2012) · Cell Transplantation · doi:10.3727/096368912x647234 · Cited by 107 · see citing works
Mifune, Y., Matsumoto, T., Takayama, K., Terada, S., Sekiya, N., Kuroda, R., Kurosaka, M., Fu, F. H., & Huard, J. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.013 · Cited by 94 · see citing works
Therapeutic Mechanisms of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model
Lee, S. Y., Kwon, B., Lee, K., Son, Y. H., & Chung, S. G. (2017) · The American Journal of Sports Medicine · doi:10.1177/0363546517689874 · Cited by 85 · see citing works
Tischer, T., Vogt, S., Aryee, S., Steinhauser, E., Adamczyk, C., Milz, S., Martinek, V., & Imhoff, A. B. (2007) · Archives of Orthopaedic and Trauma Surgery · doi:10.1007/s00402-007-0320-0 · Cited by 84 · see citing works
Endoligamentous Revascularization of an Anterior Cruciate Ligament Graft
Unterhauser, F. N., Bail, H. J., H??her, J., Haas, N. P., & Weiler, A. (2003) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000079442.64912.51 · Cited by 78 · see citing works
Martinello, T., Bronzini, I., Volpin, A., Vindigni, V., Maccatrozzo, L., Caporale, G., Bassetto, F., & Patruno, M. (2012) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.1557 · Cited by 77 · see citing works
Tashiro, Y., Gale, T. H., Sundaram, V. H., Nagai, K., Irrgang, J. J., Anderst, W. J., Nakashima, Y., Tashman, S., & Fu, F. H. (2017) · The American Journal of Sports Medicine · doi:10.1177/0363546517698676 · Cited by 72 · see citing works
Decellularized Tendon Extracellular Matrix—A Valuable Approach for Tendon Reconstruction?
Schulze-Tanzil, G. G., Al-Sadi, O., Ertel, W., & Lohan, A. (2012) · Cells · doi:10.3390/cells1041010 · Cited by 64 · see citing works
Omae, H., Sun, Y. L., An, K., Amadio, P. C., & Zhao, C. (2011) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.423 · Cited by 58 · see citing works
Flexor Tendon Tissue Engineering: Acellularized and Reseeded Tendon Constructs
Chong, A. K. S., Riboh, J. C., Smith, R. L., Lindsey, D. P., Pham, H. M., & Chang, J. (2009) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0b013e3181a65ae7 · Cited by 55 · see citing works
Norelli, J. B., Plaza, D. P., Stal, D. N., Varghese, A. M., Liang, H., & Grande, D. A. (2018) · Journal of Tissue Engineering · doi:10.1177/2041731418811183 · Cited by 53 · see citing works
Lee, D. W., Shim, J. C., Yang, S. J., Cho, S. I., & Kim, J. G. (2019) · Clinics in Orthopedic Surgery · doi:10.4055/cios.2019.11.1.60 · Cited by 52 · see citing works
Tissue-engineered intrasynovial tendons: Optimization of acellularization and seeding
Zhang, A. Y., Bates, S. R., Morrow, E. H., Pham, H. M., Pham, B. V., & Chang, J. (2009) · The Journal of Rehabilitation Research and Development · doi:10.1682/jrrd.2008.07.0086 · Cited by 49 · see citing works
Grässel, S., Stöckl, S., & Jenei‐Lanzl, Z. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-815-3_14 · Cited by 40 · see citing works
Durgam, S. S., Stewart, A. A., Pondenis, H. C., Gutierrez-Nibeyro, S. M., Evans, R. B., & Stewart, M. C. (2011) · American Journal of Veterinary Research · doi:10.2460/ajvr.73.1.153 · Cited by 40 · see citing works
Zhang, B., Luo, Q., Halim, A., Ju, Y., MORITA, Y., & Song, G. (2017) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x12666170502102423 · Cited by 24 · see citing works
Decellularized porcine xenograft for anterior cruciate ligament reconstruction
Hexter, A. T., Hing, K. A., Haddad, F. S., & Blunn, G. W. (2020) · Bone and Joint Research · doi:10.1302/2046-3758.96.bjr-2020-0030.r2 · Cited by 21 · see citing works
Lu, C., Chou, S., Shen, P., Chou, P., Ho, M., & Tien, Y. (2020) · Bone and Joint Research · doi:10.1302/2046-3758.98.bjr-2019-0365.r1 · Cited by 21 · see citing works
The TNF-NF-κB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis
Jo, S., Nam, B., Lee, Y. L., Park, H., Weon, S., Choi, S., Park, Y., & Kim, T. (2021) · Journal of Rheumatic Diseases · doi:10.4078/jrd.2021.28.4.216 · Cited by 20 · see citing works
Self-citationLee, J. K., Jo, S., Lee, Y. L., Park, H., Song, J.-S., Sung, I.-H., & Kim, T.-H. (2020) · Scientific Reports · doi:10.1038/s41598-020-60047-w · Cited by 19 · see citing works
Self-citationAhn, G.-Y., Nam, I.-H., Lee, Y. H., Lee, Y. S., Choi, Y. D., Lee, H. H., & Hwang, S. H. (2018) · Clinics in Orthopedic Surgery · doi:10.4055/cios.2018.10.4.413 · Cited by 14 · see citing works
Petri, M., Kruppa, C. G., Haasper, C., Broese, M., Liodakis, E., Krettek, C., Hurschler, C., & Jagodzinski, M. (2011) · Technology and Health Care · doi:10.3233/thc-2011-0621 · Cited by 11 · see citing works
Kim, S., Jung, J. H., Song, J.-H., & Bae, J. (2019) · Knee Surgery and Related Research · doi:10.1186/s43019-019-0005-3 · Cited by 11 · see citing works
Graft considerations for successful anterior cruciate ligament reconstruction
Kyung, H.-S. (2019) · Knee Surgery and Related Research · doi:10.1186/s43019-019-0003-5 · Cited by 9 · see citing works
The importance of plasmin for the healing of the anterior cruciate ligament
Bakırcı, E., Tschan, K., May, R. D., Ahmad, S. S., Kleer, B., & Gantenbein, B. (2020) · Bone and Joint Research · doi:10.1302/2046-3758.99.bjr-2020-0048.r1 · Cited by 8 · see citing works
Yu, Y., Ding, C., Cai, Z.-N., & Chen, X. (1986) · Mutation Research Letters · doi:10.1016/0165-7992(86)90157-0 · Cited by 8 · see citing works
Lee, J. K., Jo, S., Lee, Y. L., Weon, S., Song, J.-S., Sung, I., & Kim, T. (2021) · Cells · doi:10.3390/cells10040740 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
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Sorted by citations
Anjum, S., Li, T., Saeed, M., & Ao, Q. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127891 · Cited by 21 · see citing works
ACL injury management: a comprehensive review of novel biotherapeutics
Yu, X., Hu, J., Li, Y., Yu, W. L., & Li, B. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1455225 · Cited by 13 · see citing works
Huang, Q.-M., Zhuo, Y., Duan, Z.-X., Long, Y.-L., Wang, J.-N., Zhang, Z.-H., Fan, S.-Y., Huang, Y.-M., Deng, K.-Y., & Xin, H. (2024) · Bone and Joint Research · doi:10.1302/2046-3758.1312.bjr-2024-0136.r2 · Cited by 11 · see citing works
Tan, J., Liu, X., Zhou, M., Wang, F., Ma, L., Tang, H., He, G., Kang, X., Bian, X., & Tang, K. (2023) · Bone and Joint Research · doi:10.1302/2046-3758.125.bjr-2022-0340.r2 · Cited by 11 · see citing works
Data, K., Kulus, M., Ziemak, H., Chwarzyński, M., Piotrowska‐Kempisty, H., Bukowska, D., Antosik, P., Mozdziak, P. E., & Kempisty, B. (2023) · Cells · doi:10.3390/cells12182293 · Cited by 7 · see citing works
Park, J. H., Soh, H., Jo, S., Weon, S., Lee, S. H., Park, J.-A., Lee, M.-K., Kim, T., Sung, I., & Lee, J. K. (2023) · iScience · doi:10.1016/j.isci.2023.108521 · Cited by 6 · see citing works
Self-citationJo, S., Lee, S. H., Jeon, C., Jo, H.-R., You, Y. J., Lee, J. K., Sung, I., Kim, T., & Lee, C. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122204 · Cited by 6 · see citing works
Self-citationLo, H. L., Huang, Y., Lin, Y., Li, W., Wu, S. C., Chou, P., & Lu, C. (2025) · Bone and Joint Research · doi:10.1302/2046-3758.149.bjr-2025-0186 · Cited by 4 · see citing works
Park, J., Soh, H., Jang, Y.-K., Lee, Y. S., Lee, M.-K., Kim, H., Kim, T.-H., Alkhelaifi, K., Kim, T.-J., & Lee, J. K. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04760-1 · Cited by 3 · see citing works
Self-citationYao, P., Yang, Y., Yuan, F., Lin, Z., Qin, Y., Liu, S., Mao, Y., Wang, L., Du, R., Xu, Y., et al. (2026) · Biomaterials · doi:10.1016/j.biomaterials.2026.123977 · Cited by 2 · see citing works
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Marmotti, A., Coco, M., Orso, F., Mangiavini, L., de Girolamo, L., Bellato, E., Viganò, M., Ragni, E., Setti, S., Taverna, D., et al. (2026) · Bone and Joint Research · doi:10.1302/2046-3758.152.bjr-2024-0550.r2 · Cited by 1 · see citing works
Park, J., Kim, T.-H., & Lee, J. K. (2026) · Cells Tissues Organs · doi:10.1159/cto/acbag001
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- Authors
- Park, J., Jo, S., Lee, M.-K., Kim, T.-H., Sung, I.-H., & Lee, J. K.
- Affiliations
- Hanyang University (KR)
- Department of Research and Development, Korea Public Tissue Bank, Seongnam-si, South Korea
- Hanyang University Seoul Hospital (KR)
- Corresponding author
- Lee, Jin K.
- Venue
- Bone & Joint Research
- Published
- 2022-11-01
- Volume
- 11
- Issue
- 11
- Pages
- 777-786
- ISSN
- 2046-3758 (ISSN-L)
- PMC
- PMC9680201
- OpenAlex
- W4308367072
- Cited by
- 12
- References
- 51
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 5
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bone and Joint Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation (2021R1A6A1A03038899)
- National Research Foundation of Korea (2021R1A6A1A03038899, 2020R1F1A1049719, 2020R1A2C1102386)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- adipose-derived stem cells, ligamentization, type I collagen, type III collagen, extracellular matrix, anterior cruciate ligament reconstruction, cell therapy
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