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Umbilical cord mesenchymal stem cells combined with secretome for treating congenital pseudarthrosis of the Tibia: a case series

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Abstract

Introduction

Most patients with congenital pseudoarthrosis of tibia (CPT) do not have promising outcomes despite multiple attempts using conventional surgeries. The combination of umbilical cord-derived mesenchymal stem cells and conditioned medium (secretome) contains major components pivotal for the enhancement of fracture healing. The purpose of this study was to address fracture healing in CPT cases that were treated using the combined implantation of umbilical-cord mesenchymal stem cells (UC-MSCs) and secretome.

Materials and Methods

From 2016 to 2017, six patients with CPT who were treated by one senior pediatric orthopedic consultant at a single center (3 girls and 3 boys; mean age of 5.8 years) were included in this case series. A combined procedure including resection of hamartomatous fibrotic tissue, implantation of MSCs and secretome, and fixation using a locking plate and screws was performed. Patients were followed up for a mean of 29 months. Leg-length discrepancy, refracture rate, functional outcome, and radiological outcomes were assessed preoperatively, immediately postoperatively and at the final follow-up.

Result

Five out of 6 (83%) of the patients experienced primary union. One patient experienced refracture; however, 8 months later, after another implantation and reconstruction were performed, union eventually occurred. Significant functional improvement was achieved after at least 1 year of follow-up.

Conclusion

This case series suggests that the combination of secretome and UC-MSCs is a potential treatment for CPT, it highlights the efficacy of the combined procedure in treating CPT and in achieving satisfying results. A larger number of subjects and longer follow-up are required for further study.

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References

  1. Agha RA, Borrelli MR, Farwana R, Koshy K, Fowler AJ, Orgill DP (2018) The PROCESS 2018 statement: updating consensus preferred reporting of CasE series in surgery (PROCESS) guidelines. Int J Surg 60:279–282. https://doi.org/10.1016/j.ijsu.2018.10.031

    Article  PubMed  Google Scholar 

  2. Cho T, Seo J, Hr L, Wj Y, Cy C, Ih C (2008) Biologic characteristics of fibrous hamartoma from congenital pseudarthrosis of the tibia associated. J Bone Joint Surgery Am 90:2735–2744. https://doi.org/10.2106/JBJS.H.00014

    Article  Google Scholar 

  3. Das SP, Ganesh S, Pradhan S, Singh D, Mohanty RN (2014) Effectiveness of recombinant human bone morphogenetic protein-7 in the management of congenital pseudoarthrosis of the tibia: a randomised controlled trial. Int Orthop 38(9):1987–1992. https://doi.org/10.1007/s00264-014-2361-7

    Article  PubMed  Google Scholar 

  4. Dilogo IH, Mujadid F, Nurhayati RW, Kurniawan A (2018) Evaluation of bone marrow-derived mesenchymal stem cell quality from patients with congenital pseudoarthrosis of the tibia. J Orthop Surg Res 9:9–16

    Google Scholar 

  5. Dobbs MB, Rich MM, Gordon JE, Szymanski DA, Schoenecker PL (2005) Use of an intramedullary rod for the treatment of congenital pseudarthrosis of the tibia. J Bone Joint Surg– Ser A 87(SUPPL. 1):33–40. https://doi.org/10.2106/00004623-200503001-00003

    Article  Google Scholar 

  6. Dohin B, Kohler R (2012) Masquelet’s procedure and bone morphogenetic protein in congenital pseudarthrosis of the tibia in children: a case series and meta-analysis. J Children’s Orthop 6(4):297–306. https://doi.org/10.1007/s11832-012-0421-3

    Article  Google Scholar 

  7. Donnell CO, Foster J, Mooney R, Beebe C, Donaldson N, Heare T (2017) Congenital pseudarthrosis of the Tibia. JBJS Rev 5(4):1–12

    Google Scholar 

  8. Giannoudis PV, Einhorn TA, Marsh D (2007) Fracture healing: the diamond concept. Injury 38(4 SUPPL.):11–12. https://doi.org/10.1016/S0020-1383(08)70003-2

    Article  Google Scholar 

  9. Horn J, Steen H, Terjesen T (2013) Epidemiology and treatment outcome of congenital pseudarthrosis of the tibia. J Children’s Orthop 7(2):157–166. https://doi.org/10.1007/s11832-012-0477-0

    Article  Google Scholar 

  10. Ismail HD, Phedy P, Kholinne E, Djaja YP, Kusnadi Y, Merlina M, Yulisa ND (2016) Mesenchymal stem cell implantation in atrophic nonunion of the long bones: a translational study. Bone Joint Res 5(7):287–293. https://doi.org/10.1302/2046-3758.57.2000587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Katagiri W, Osugi M, Kawai T, Hibi H (2016) First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head Face Med 12(1):1–10. https://doi.org/10.1186/s13005-016-0101-5

    Article  Google Scholar 

  12. Kim HO, Choi S, Kim H (2013) | Feature article | mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders. Tissue Eng Regen Med 10(3):93–101. https://doi.org/10.1007/s13770-013-0010-7

    Article  CAS  Google Scholar 

  13. Marsell R, Einhorn TA (2011) The biology of fracture healing. Injury 42(6):551–555. https://doi.org/10.1016/j.injury.2011.03.031

    Article  PubMed  PubMed Central  Google Scholar 

  14. Oetgen ME, Richards BS (2010) Complications associated with the use of bone morphogenetic protein in pediatric patients. J Pediatric Orthop 30(2):192–198. https://doi.org/10.1097/BPO.0b013e3181d075ab

    Article  Google Scholar 

  15. Ohnishi I, Sato W, Matsuyama J, Yajima H, Haga N, Kamegaya M, Minami A, Sato M, Yoshino S, Oki T, Nakamura K (2005) Treatment of congenital pseudarthrosis of the Tibia. J Pediatric Orthop 25(2):219–224. https://doi.org/10.1097/01.bpo.0000151054.54732.0b

    Article  Google Scholar 

  16. Paley D (2006) Congenital pseudarthrosis of the Tibia. Curr Progr Orthop, NA. 247:317–348. https://doi.org/10.1097/00003086-198910000-00008

    Article  Google Scholar 

  17. Pannier S (2011) Congenital pseudarthrosis of the tibia. Orthop Traumatol Surg Res 97(7):750–761. https://doi.org/10.1016/j.otsr.2011.09.001

    Article  CAS  PubMed  Google Scholar 

  18. Patwa J, Patel R (2013) A short series of congenital pseudoarthrosis tibia. J Orthop 10(3):123–132. https://doi.org/10.1016/j.jor.2013.07.002

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pawitan JA (2014) Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int 2014:1–14. https://doi.org/10.1155/2014/965849

    Article  CAS  Google Scholar 

  20. Pawitan JA, Liem IK, Budiyanti E, Fasha I, Feroniasanti L, Jamaan T, Sumapradja K (2014) Umbilical cord derived stem cell culture: multiple-harvest explant method. Int J PharmTech Res 6(4):1202–1208. https://doi.org/10.1371/journal.pcbi.1003775

    Article  CAS  Google Scholar 

  21. Richards BS, Oetgen ME, Johnston CE (2010) The use of rhBMP-2 for the treatment of congenital pseudarthrosis of the Tibia: a case series. J Bone Joint Surg- Ser A 92(1):177–185. https://doi.org/10.2106/JBJS.H.01667

    Article  Google Scholar 

  22. Vander Have KL, Hensinger RN, Caird M, Johnston C, Farleya F (2008) Congenital pseudarthrosis of the tibia. J Am Acad Orthop Surg 16(4):228–236. https://doi.org/10.1016/j.rcot.2009.12.008

    Article  PubMed  Google Scholar 

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Funding

This research was funded by the postgraduate research grant Universitas Indonesia (Grant number: 01/PKS/IPT/INSENTIF/IV/2019).

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Correspondence to Witantra Dhamar Hutami.

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Kurniawan, A., Ivansyah, M.D., Dilogo, I.H. et al. Umbilical cord mesenchymal stem cells combined with secretome for treating congenital pseudarthrosis of the Tibia: a case series. Eur J Orthop Surg Traumatol 33, 2881–2888 (2023). https://doi.org/10.1007/s00590-023-03511-3

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