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Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects

Yıl 2023, Cilt: 27 Sayı: 5, 1866 - 1874, 28.06.2025

Mansooreh Mirzaei Reza Eshaghi-gorji Elahe Maleki Abbasali Karimpour Malekshah Fereshteh Talebpour Amiri

Öz

Mesenchymal stem cell-secreted factors play influential roles in proliferation, differentiation, and chondrogenesis. This study was designed to examine the ameliorative effects of conditioned medium (CM) from stem cells, fibroblasts, and platelet rich plasma (PRP) on articular cartilage defects in a rat model. A cartilage defect (2 mm in diameter) was created in the intercondylar notch of the femur. Forty adult male Wistar rats were divided into eight groups: intact, sham, and untreated, DMEM, stem cells, stem cell conditioned medium, fibroblast conditioned medium, and PRP. Conditioned medium, PRP, and stem cells were administered as a single dose intra-articularly immediately after surgery and closure of the joint capsule. At the end of the 4th week, cartilage repair was assessed by histopathological assays. Microscopy data showed that defects in the stem cell-conditioned medium group repaired tissue better in terms of cartilage layer formation, thickness, collagen deposition and glycosaminoglycan synthesis compared to defects in the stem cell, fibroblast-conditioned medium, and PRP groups. In terms of angiogenesis, the fibroblast-conditioned medium group outperformed the other groups. Based on histological findings, stem cell conditioned medium yields superior results to fibroblast conditioned medium and PRP treatment in creating hyaline-like repair tissue. The effectiveness of the role of conditioned medium compared to cell therapy may only be due to the type and amount of growth factors present in them.

Anahtar Kelimeler

Stem cell-conditioned medium fibroblast-conditioned medium cartilage defect cartilage repair.

Kaynakça

  • [1] Chen TM, Chen YH, Sun HS, Tsai SJ. Fibroblast growth factors: Potential novel targets for regenerative therapy of osteoarthritis. Chinese Journal of Physiology. 2019; 62(1). https://doi.org/10.4103/cjp.cjp_11_19
  • [2] Li L, Duan X, Fan Z, Chen L, Xing F, Xu Z, Chen Q, Xiang Z. Mesenchymal stem cells in combination with hyaluronic acid for articular cartilage defects. Scientific Reports. 2018; 8(1): 1–11. https://doi.org/10.1038/s41598-018-27737-y
  • [3] Li Y, Liu Y, Guo Q. Silk fibroin hydrogel scaffolds incorporated with chitosan nanoparticles repair articular cartilage defects by regulating TGF-β1 and BMP-2. Arthritis Research & Therapy. 2021; 23(1): 1–11. https://doi.org/10.1186/s13075-020-02382-x
  • [4] Thorp H, Kim K, Kondo M, Maak T, Grainger DW, Okano T. Trends in articular cartilage tissue engineering: 3D mesenchymal stem cell sheets as candidates for engineered hyaline-like cartilage. Cells. 2021; 10(3): 643. https://doi.org/10.3390/cells10030643
  • [5] Matthews JR, Chauhan K, Brutico JM, Abraham DT, Heard JC, Tucker BS, Tjoumakaris FP, Freedman KB. Differences in clinical and functional outcomes between osteochondral allograft transplantation and autologous chondrocyte implantation for the treatment of focal articular cartilage defects. Orthopaedic Journal of Sports Medicine. 2022; 10(2): 23259671211058425. https://doi.org/10.1177/23259671221102062
  • [6] Petrigliano FA, Liu NQ, Lee S, et al. Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes. NPJ Regenerative Medicine. 2021; 6(1): 1–14. https://doi.org/10.1101/2021.05.27.446024
  • [7] Hingert D, Nawilaijaroen P, Aldridge J, Baranto A, Brisby H. Investigation of the effect of secreted factors from mesenchymal stem cells on disc cells from degenerated discs. Cells Tissues Organs. 2019; 208(1–2): 76–88. https://doi.org/10.1159/000506350
  • [8] Vinod E, Padmaja K, Kachroo U. Effect of human articular chondroprogenitor derived conditioned media on chondrogenic potential of bone marrow derived mesenchymal stromal cells. Journal of Orthopaedics, Trauma and Rehabilitation. 2021; 28: 22104917211006885. https://doi.org/10.1177/22104917211006885
  • [9] Ehrenfest DMD, Lemo N, Jimbo R, Sammartino G. Selecting a relevant animal model for testing the in vivo effects of Choukroun's platelet-rich fibrin (PRF): rabbit tricks and traps. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 110(4): 413–6. https://doi.org/10.1016/j.tripleo.2010.05.057
  • [10] Lam J, Lu S, Kasper FK, Mikos AG. Strategies for controlled delivery of biologics for cartilage repair. Advanced Drug Delivery Reviews. 2015; 84: 123–34. https://doi.org/10.1016/j.addr.2014.06.006
  • [11] Wang J, Liu S, Li J, Yi Z. The role of the fibroblast growth factor family in bone‐related diseases. Chemical Biology & Drug Design. 2019; 94(4): 1740–9. https://doi.org/10.1111/cbdd.13588
  • [12] Endo K, Fujita N, Nakagawa T, Nishimura R. Effect of fibroblast growth factor-2 and serum on canine mesenchymal stem cell chondrogenesis. Tissue Engineering Part A. 2019; 25(11–12): 901–10. https://doi.org/10.1089/ten.tea.2018.0177
  • [13] Lee CS, Burnsed OA, Raghuram V, et al. Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem Cell Research & Therapy. 2012; 3(4): 1–13. https://doi.org/10.3410/f.717960435.793463489
  • [14] Chatterjee A, Agarwal P, Subbaiah SK. Platelet rich fibrin: an autologous bioactive membrane. Apollo Medicine. 2014; 11(1): 24–6. https://doi.org/10.1016/j.apme.2014.01.007
  • [15] Chen KS, Chien KC, Huang YS, Chang CLT, Chang SC. Proliferative effect of platelet-rich fibrin on canine bone marrow-derived stromal cells. Taiwan Veterinary Journal. 2014; 40(3): 151–61. https://doi.org/10.1142/s1682648514500176
  • [16] Ehrenfest DMD, Doglioli P, de Peppo GM, Del Corso M, Charrier JB. Choukroun's platelet-rich fibrin (PRF) stimulates in vitro proliferation and differentiation of human oral bone mesenchymal stem cell in a dose-dependent way. Archives of Oral Biology. 2010; 55(3): 185–94. https://doi.org/10.1016/j.archoralbio.2010.01.004
  • [17] Hur W, Lee HY, Min HS, et al. Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium. Stem Cell Research & Therapy. 2017; 8(1): 1–13. https://doi.org/10.1186/s13287-017-0520-7
  • [18] Zhang Y, Zhang J, Chang F, Xu W, Ding J. Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel. Materials Science and Engineering: C. 2018; 88: 79–87. https://doi.org/10.1016/j.msec.2018.02.028
  • [19] Cucchiarini M, Madry H, Ma C, et al. Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Molecular Therapy. 2005; 12(2): 229–38. https://doi.org/10.1016/j.ymthe.2005.03.012
  • [20] Chen W, Sun Y, Gu X, et al. Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model. Journal of Tissue Engineering and Regenerative Medicine. 2019; 13(9): 1618–28. https://doi.org/10.1002/term.2916
  • [21] Ogasawara N, Kano F, Hashimoto N, et al. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis. Osteoarthritis and Cartilage. 2020; 28(6): 831–41. https://doi.org/10.1016/j.joca.2020.03.010
  • [22] Molgat ASD, Gagnon AM, Sorisky A. Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner. Am J Physiol Cell Physiol. 2009; 296(4): C757–C765. https://doi.org/10.1152/ajpcell.00617.2008
  • [23] Amirjamshidi H, Milani BY, Sagha HM, et al. Limbal fibroblast conditioned media: a non-invasive treatment for limbal stem cell deficiency. Molecular Vision. 2011; 17: 658.
  • [24] Li Z, Weng X. Platelet-rich plasma use in meniscus repair treatment: a systematic review and meta-analysis. Journal of Orthopaedic Surgery and Research. 2022; 17(1): 1–14. https://doi.org/10.1186/s13018-022-03293-0
  • [25] Li Z, Bi Y, Wu Q, et al. A composite scaffold of Wharton’s jelly and chondroitin sulphate loaded with human umbilical cord mesenchymal stem cells repairs articular cartilage defects. Journal of Materials Science: Materials in Medicine. 2021; 32(4): 1–11. https://doi.org/10.1007/s10856-021-06506-w
  • [26] El-Rahman SSA, Amer MS, Hassan MH, et al. Repair of experimentally induced femoral chondral defect in a rabbit model using Lyophilized growth promoting factor extracted from horse blood platelets (L-GFequina). Injury. 2022; 53(4): 1375–84. https://doi.org/10.1016/j.injury.2022.02.004
  • [27] Kazemi D, Shams Asenjan K, Dehdilani N, Parsa H. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin. Bone & Joint Research. 2017; 6(2): 98–107. https://doi.org/10.1302/2046-3758.62.bjr-2016-0188.r1

Yıl 2023, Cilt: 27 Sayı: 5, 1866 - 1874, 28.06.2025

Mansooreh Mirzaei Reza Eshaghi-gorji Elahe Maleki Abbasali Karimpour Malekshah Fereshteh Talebpour Amiri

Öz

Kaynakça

  • [1] Chen TM, Chen YH, Sun HS, Tsai SJ. Fibroblast growth factors: Potential novel targets for regenerative therapy of osteoarthritis. Chinese Journal of Physiology. 2019; 62(1). https://doi.org/10.4103/cjp.cjp_11_19
  • [2] Li L, Duan X, Fan Z, Chen L, Xing F, Xu Z, Chen Q, Xiang Z. Mesenchymal stem cells in combination with hyaluronic acid for articular cartilage defects. Scientific Reports. 2018; 8(1): 1–11. https://doi.org/10.1038/s41598-018-27737-y
  • [3] Li Y, Liu Y, Guo Q. Silk fibroin hydrogel scaffolds incorporated with chitosan nanoparticles repair articular cartilage defects by regulating TGF-β1 and BMP-2. Arthritis Research & Therapy. 2021; 23(1): 1–11. https://doi.org/10.1186/s13075-020-02382-x
  • [4] Thorp H, Kim K, Kondo M, Maak T, Grainger DW, Okano T. Trends in articular cartilage tissue engineering: 3D mesenchymal stem cell sheets as candidates for engineered hyaline-like cartilage. Cells. 2021; 10(3): 643. https://doi.org/10.3390/cells10030643
  • [5] Matthews JR, Chauhan K, Brutico JM, Abraham DT, Heard JC, Tucker BS, Tjoumakaris FP, Freedman KB. Differences in clinical and functional outcomes between osteochondral allograft transplantation and autologous chondrocyte implantation for the treatment of focal articular cartilage defects. Orthopaedic Journal of Sports Medicine. 2022; 10(2): 23259671211058425. https://doi.org/10.1177/23259671221102062
  • [6] Petrigliano FA, Liu NQ, Lee S, et al. Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes. NPJ Regenerative Medicine. 2021; 6(1): 1–14. https://doi.org/10.1101/2021.05.27.446024
  • [7] Hingert D, Nawilaijaroen P, Aldridge J, Baranto A, Brisby H. Investigation of the effect of secreted factors from mesenchymal stem cells on disc cells from degenerated discs. Cells Tissues Organs. 2019; 208(1–2): 76–88. https://doi.org/10.1159/000506350
  • [8] Vinod E, Padmaja K, Kachroo U. Effect of human articular chondroprogenitor derived conditioned media on chondrogenic potential of bone marrow derived mesenchymal stromal cells. Journal of Orthopaedics, Trauma and Rehabilitation. 2021; 28: 22104917211006885. https://doi.org/10.1177/22104917211006885
  • [9] Ehrenfest DMD, Lemo N, Jimbo R, Sammartino G. Selecting a relevant animal model for testing the in vivo effects of Choukroun's platelet-rich fibrin (PRF): rabbit tricks and traps. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 110(4): 413–6. https://doi.org/10.1016/j.tripleo.2010.05.057
  • [10] Lam J, Lu S, Kasper FK, Mikos AG. Strategies for controlled delivery of biologics for cartilage repair. Advanced Drug Delivery Reviews. 2015; 84: 123–34. https://doi.org/10.1016/j.addr.2014.06.006
  • [11] Wang J, Liu S, Li J, Yi Z. The role of the fibroblast growth factor family in bone‐related diseases. Chemical Biology & Drug Design. 2019; 94(4): 1740–9. https://doi.org/10.1111/cbdd.13588
  • [12] Endo K, Fujita N, Nakagawa T, Nishimura R. Effect of fibroblast growth factor-2 and serum on canine mesenchymal stem cell chondrogenesis. Tissue Engineering Part A. 2019; 25(11–12): 901–10. https://doi.org/10.1089/ten.tea.2018.0177
  • [13] Lee CS, Burnsed OA, Raghuram V, et al. Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem Cell Research & Therapy. 2012; 3(4): 1–13. https://doi.org/10.3410/f.717960435.793463489
  • [14] Chatterjee A, Agarwal P, Subbaiah SK. Platelet rich fibrin: an autologous bioactive membrane. Apollo Medicine. 2014; 11(1): 24–6. https://doi.org/10.1016/j.apme.2014.01.007
  • [15] Chen KS, Chien KC, Huang YS, Chang CLT, Chang SC. Proliferative effect of platelet-rich fibrin on canine bone marrow-derived stromal cells. Taiwan Veterinary Journal. 2014; 40(3): 151–61. https://doi.org/10.1142/s1682648514500176
  • [16] Ehrenfest DMD, Doglioli P, de Peppo GM, Del Corso M, Charrier JB. Choukroun's platelet-rich fibrin (PRF) stimulates in vitro proliferation and differentiation of human oral bone mesenchymal stem cell in a dose-dependent way. Archives of Oral Biology. 2010; 55(3): 185–94. https://doi.org/10.1016/j.archoralbio.2010.01.004
  • [17] Hur W, Lee HY, Min HS, et al. Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium. Stem Cell Research & Therapy. 2017; 8(1): 1–13. https://doi.org/10.1186/s13287-017-0520-7
  • [18] Zhang Y, Zhang J, Chang F, Xu W, Ding J. Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel. Materials Science and Engineering: C. 2018; 88: 79–87. https://doi.org/10.1016/j.msec.2018.02.028
  • [19] Cucchiarini M, Madry H, Ma C, et al. Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Molecular Therapy. 2005; 12(2): 229–38. https://doi.org/10.1016/j.ymthe.2005.03.012
  • [20] Chen W, Sun Y, Gu X, et al. Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model. Journal of Tissue Engineering and Regenerative Medicine. 2019; 13(9): 1618–28. https://doi.org/10.1002/term.2916
  • [21] Ogasawara N, Kano F, Hashimoto N, et al. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis. Osteoarthritis and Cartilage. 2020; 28(6): 831–41. https://doi.org/10.1016/j.joca.2020.03.010
  • [22] Molgat ASD, Gagnon AM, Sorisky A. Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner. Am J Physiol Cell Physiol. 2009; 296(4): C757–C765. https://doi.org/10.1152/ajpcell.00617.2008
  • [23] Amirjamshidi H, Milani BY, Sagha HM, et al. Limbal fibroblast conditioned media: a non-invasive treatment for limbal stem cell deficiency. Molecular Vision. 2011; 17: 658.
  • [24] Li Z, Weng X. Platelet-rich plasma use in meniscus repair treatment: a systematic review and meta-analysis. Journal of Orthopaedic Surgery and Research. 2022; 17(1): 1–14. https://doi.org/10.1186/s13018-022-03293-0
  • [25] Li Z, Bi Y, Wu Q, et al. A composite scaffold of Wharton’s jelly and chondroitin sulphate loaded with human umbilical cord mesenchymal stem cells repairs articular cartilage defects. Journal of Materials Science: Materials in Medicine. 2021; 32(4): 1–11. https://doi.org/10.1007/s10856-021-06506-w
  • [26] El-Rahman SSA, Amer MS, Hassan MH, et al. Repair of experimentally induced femoral chondral defect in a rabbit model using Lyophilized growth promoting factor extracted from horse blood platelets (L-GFequina). Injury. 2022; 53(4): 1375–84. https://doi.org/10.1016/j.injury.2022.02.004
  • [27] Kazemi D, Shams Asenjan K, Dehdilani N, Parsa H. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin. Bone & Joint Research. 2017; 6(2): 98–107. https://doi.org/10.1302/2046-3758.62.bjr-2016-0188.r1
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Mansooreh Mirzaei 0000-0001-9851-3100

Reza Eshaghi-gorji 0000-0002-7187-6646

Elahe Maleki 0000-0002-8357-7547

Abbasali Karimpour Malekshah 0000-0002-9649-2235

Fereshteh Talebpour Amiri

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 5

Kaynak Göster

APA Mirzaei, M., Eshaghi-gorji, R., Maleki, E., Malekshah, A. K., vd. (2025). Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects. Journal of Research in Pharmacy, 27(5), 1866-1874.
AMA Mirzaei M, Eshaghi-gorji R, Maleki E, Malekshah AK, Amiri FT. Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects. J. Res. Pharm. Temmuz 2025;27(5):1866-1874.
Chicago Mirzaei, Mansooreh, Reza Eshaghi-gorji, Elahe Maleki, Abbasali Karimpour Malekshah, ve Fereshteh Talebpour Amiri. “Investigating the Comparative Effect of Conditioned Medium from Mesenchymal Stem Cells and Fibroblast Cells on Articular Cartilage Defects”. Journal of Research in Pharmacy 27, sy. 5 (Temmuz 2025): 1866-74.
EndNote Mirzaei M, Eshaghi-gorji R, Maleki E, Malekshah AK, Amiri FT (01 Temmuz 2025) Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects. Journal of Research in Pharmacy 27 5 1866–1874.
IEEE M. Mirzaei, R. Eshaghi-gorji, E. Maleki, A. K. Malekshah, ve F. T. Amiri, “Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects”, J. Res. Pharm., c. 27, sy. 5, ss. 1866–1874, 2025.
ISNAD Mirzaei, Mansooreh vd. “Investigating the Comparative Effect of Conditioned Medium from Mesenchymal Stem Cells and Fibroblast Cells on Articular Cartilage Defects”. Journal of Research in Pharmacy 27/5 (Temmuz 2025), 1866-1874.
JAMA Mirzaei M, Eshaghi-gorji R, Maleki E, Malekshah AK, Amiri FT. Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects. J. Res. Pharm. 2025;27:1866–1874.
MLA Mirzaei, Mansooreh vd. “Investigating the Comparative Effect of Conditioned Medium from Mesenchymal Stem Cells and Fibroblast Cells on Articular Cartilage Defects”. Journal of Research in Pharmacy, c. 27, sy. 5, 2025, ss. 1866-74.
Vancouver Mirzaei M, Eshaghi-gorji R, Maleki E, Malekshah AK, Amiri FT. Investigating the comparative effect of conditioned medium from mesenchymal stem cells and fibroblast cells on articular cartilage defects. J. Res. Pharm. 2025;27(5):1866-74.