نویسندگان

1 استادیار، دانشگاه علوم پزشکی مشهد، مشهد، ایران.

2 دانشیار، دانشگاه علوم پزشکی مشهد، مشهد، ایران.

3 فارماکولوژیست پژوهشکده بوعلی دانشگاه علوم پزشکی مشهد، مشهد، ایران.

چکیده

ٰ
چکیده
مقدمه: «جوش‌ناخوردگی» (nonunion)، یک عارضة جدی به دنبال شکستگی‌ استخوان‌های بلند است که چالش بزرگی برای جراحان ارتوپد به همراه دارد. این نوع شکستگی‌ها عوارض زیادی به دنبال دارند. فاکتورهای تحریک‌کنندة استخوان‌سازی، همراه با بهبود شرایط مکانیکال محیطی می‎توانند سرعت جوش‌خوردن را افزایش دهند. در این مطالعه، هدف ما درمان جوش‌ناخوردگی به کمک سلول‌های تک‌هسته‌ای به دست آمده از مغز استخوان، BMDMC (bone marrow-derived mononuclear cell) و تغلیظ و کاربرد آن به عنوان منشأ سلول‌های استئوپروژنیتور همراه با فیکساسیون داخلی بود.
مواد و روش‌ها: از نوامبر2010 تا می 2013، 19 بیمار با جوش‌ناخوردگی استخوان، تحت درمان با سلول تک‌هسته‌ای مشتق از مغز استخوان (BMDMC) قرار گرفتند که شامل 15 مرد و 4 زن با متوسط سنی 8/37 سال (18 تا 81 سال) بود. فاصلة زمانی بین تروما تا درمان بین 7 تا 28 ماه (میانگین 4/13 ماه) بود. ابتدا قشرزدایی اطراف محل جوش‌ناخورده انجام شد تا بستر مناسب برای سلول‌های تک‌هسته‌ای ایجاد شود. سپس 2 میلی‌لیتر مغز استخوان تغلیظ شده در محل قرار داده شدکه به صورت مخلوط با چیپس آلوگرافت کورتیکوکنسلوس دمینرالیزه بود. سرعت ترمیم به صورت بالینی و رادیولوژیک هر 4 هفته پیگیری شد.
یافته‌ها: جوش‌خوردن استخوان در 18بیمار از19 بیمار، در طول 06/1 تا 6 ماه با متوسط زمانی 5/3 ماه، به دست آمد. در طول مدت بیهوشی عارضه‌ای نداشتیم و هیچ موردی از عفونت، هماتوم یا درد مزمن در بیماران ایجاد نشد.
نتیجه‌گیری: پیوند مغز استخوان خودی با BMDMC یک درمان منطقی، مؤثر و آسان برای درمان جوش‌ناخوردگی استخوان‌های بلند مثل تیبیا و فمور بعد از فیکساسیون داخلی به شمار می‎رود.
 

کلیدواژه‌ها

عنوان مقاله [English]

Concentrated Autologous Bone Marrow-Derived Mononuclear Cells may have Positive Effect on Treatment of Long Bones Fracture Nonunion

نویسندگان [English]

  • Amin Razi 1
  • Mohammad taghi Peivandi 2
  • Ali Birjandinejad 2
  • Sara Amel Farzad 3

چکیده [English]

Abstract
Background: Nonunion is a serious complication following long-bone fracture that is known as a therapeutic challenge for surgeons and is associated with significant morbidity. It has been shown that osteogenesis stimulating factors combined with optimization of the mechanical environment could facilitate and accelerate nonunion healing. In this study, we aimed to treat nonunion using autologous bone marrow-derived mononuclear cell (BMDMC) aspirate as a source of osteoprogenitor cells combined with internal fixation.
Methods: From November 2010 to May 2013, 19 cases of nonunion were treated with bone marrow-derived mononuclear cell (BMDMC) grafting, that included 15 males and 4 females with an average age of 37.8 years (range, 18-81 years). The time from injury to therapy was 7 to 28 months, with an average of 13.4 months. At first, decortications were performed around the nonunion site to prepare a suitable bed for bone marrow grafting. Then, 2 ml of bone marrow concentrated cells was applied to the nonunion site in a mixture with partially demineralized cortical cancellous allograft chips. The healing rate in each patient was clinically and radiologically evaluated every 4 weeks.
Results: Bone union was obtained in 18 of the 19 patients during 1.06 to 6 months with an average time of 3.5 months. No complications during anesthesia nor any infection, hematoma or chronic pain at the nonunion site were observed in any patient.
Conclusion: Transplantation of autologous BMDMC aspirate is a reasonable, effective and easy treatment option for tibial and femoral nonunion after internal fixation.
Trial registration: This study has been registrated in ClinicalTrials.gov (https://clinicaltrials.gov).
TRN:NCT01788059
 

کلیدواژه‌ها [English]

  • Keywords: Fracture Ununited
  • Fracture Healing
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Bony Callus
  1. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007;38(4):S3-6.
  2. Fayaz HC, Giannoudis PV, Vrahas MS, Smith RM, Moran C, Pape HC, et al. The role of stem cells in fracture healing and nonunion. Int Orthop. 2011; 35(11):1587-97.
  3. Matthews SJ, Nikolaou VS, Giannoudis PV.Innovations in osteosynthesis and fracture care Injury. 2008; 39(8):827-38.
  4. Schoelles K, Snyder D, Kaczmarek J, Kuserk E, Erinoff E, Turkelson C, et al., editors. The Role of Bone Growth Stimulating Devices and Orthobiologics in Healing Nonunion. Rockville, MD: Agency for Healthcare Research and Quality (US). 2005; p. 156. Available from: https://www.cms.gov/Medicare/Coverage/DeterminationProcess/Downloads/id29TA.pdf.
  5. Kim SJ, Shin YW, Yang KH, Kim SB, Yoo MJ, Han SK, et al. A multi-center, randomized, clinical study to compare the effect and safety of autologous cultured osteoblast (Ossron) injection to treat fractures. BMC Musculoskelet Disord. 2009; Feb 12:10- 20.
  6. Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunion. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am .2005; 87(7) 1430-37.
  7. Matsuda Y, Sakayama K, Okumura H, Kawatani Y, Mashima N, Shibata T. Percutaneous autologous for bone marrow transplantation of the nonunion of the femur. Nihon Geka Hokan .1998; 67(1):10-17.
  8. Li Y, Shi S, Liu Z, Li Z, Wang R, Guo Y, et al .Treatment of humeral shaft nonunion with interlocking nail and percutaneous injection of bone marrow. Zhonghua Wai Ke Za Zhi. 2000; 38(10):732-5, 42.
  9. Wang L, Li WS, Zhang QS .Autogenous bone marrow graft for the management of nonunion of tibia. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2001; 15(1):24-25.
  10. Bhargava R, Sankhla S, Gupta A, Changani R, Gagal K. Percutaneous autologus bone marrow injection in the treatment of delayed or nonunion. Indian J Orthop. 2007; 41(1):67-71.
  11. Ma JT, Yu M, Zhang MC, Zhu XJ, Xu HY, Liang GJ .Clinical observation on percutaneous autologous bone marrow grafting for treatment of fracture nonunion. Zhongguo Gu Shang. 2009; 22(11):862-64.
  12. Tang ZH, Zhu LX, Xu TB, Wang K, Zhou XM, Li Q .Treatment of focal bone defect in postoperative nonunion with autologous red bone marrow injection. Zhongguo Gu Shang. 2009; 22(7):549-50.
  13. Ling HM, Wu HX, Huang CY, Ma SQ. Deep fascia composite autologous red bone marrow transplantation for the treatment of fracture nonunion. Zhongguo Gu Shang. 2009; 22(11):859-61.
  14. Braly HL, O'Connor DP, Brinker MR. Percutaneous autologous bone marrow injection in the treatment of distal meta-diaphyseal tibial nonunion and delayed unions. J Orthop Trauma. 2013; 27(9):527-33.
  15. Healey JH, Zimmerman PA, McDonnell JM, Lane JM .percutaneous bone marrow grafting of delayed union and nonunion in cancer patients. Clin Orthop Relat Res. 1990 ;( 256):280-5.
  16. Luis A. Corrales, Saam Morshed, Mohit Bhandari, Theodore Miclau, III, Variability in the Assessment of Fracture-Healing in Orthopaedic Trauma Studies. J Bone Joint Surg Am.2008; 90(9):1862–8.
  17. Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;(405):14-23.
  18. Connolly J, Guse R, Lippiello L, Dehne R. Development of an osteogenic bone-marrow preparation. 1989; 71(5):684-91.
  19. Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. J Bone Joint Surg Am.2004; 86-A (6):1153-60.
  20. Muschler GF, Nitto H, Matsukura Y, Boehm C, Valdevit A, Kambic H, et al. Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin Orthop Relat Res .2003; (407):102-18.
  21. Hernigou P, Poignard A, Manicom O, Mathieu G, Rouard H. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg Br. 2005; 87(7):896-902.
  22. Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunion. Surgical Technique. J Bone Joint Surg Am. 2006; 88 Suppl 1 Pt 2:322-7.
  23. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am. 1997; 79(11):1699-709.
  24. Muschler GF, Nitto H, Boehm CA, Easley KA. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res. 2001; 19(1):117-25.
  25. Michela Pierini, Barbara Dozza, Enrico Lucarelli, Pier Luigi Tazzari. Efficient isolation and enrichment of mesenchymal stem cells from bone marrow. Cytotherapy. 2012; 14(6):686-93.
  26. Yuhan Chang, Pang-Hsin Hsieh, Chuck C-K Chao. The efficiency of Percoll and Ficoll density gradient media in the isolation of marrow derived human mesenchymal stem cells with osteogenic potential. Chang Gung Med J. 2009; 32(3):264-75.
  27. Pingal Desai , Saad Mumtaz Hasan , Lester Zambrana. Bone Mesenchymal Stem Cells with Growth Factors Successfully Treat Nonunions and Delayed Unions. HSS J. 2015; 11(2):104-11.
  28. Valerio Sansone , Manuel Brañes , Pietro Romeo. A novel bimodal approach for treating atrophic bone non-unions with extracorporeal shockwaves and autologous mesenchymal stem cell transplant. Med Hypotheses. 2018; 111:4-7.
  29. Jean-Baptiste Gross , Jérôme Diligent , Danièle Bensoussan. Percutaneous autologous bone marrow injection for treatment of delayed and non-union of long bone: a retrospective study of 45 cases. Biomed Mater Eng. 2015; 25(1 Suppl):187-97.
  30. Ramji Lal Sahu. Percutaneous autogenous bone marrow injection for delayed union or non-union of long bone fractures after internal fixation. Rev Bras Ortop. 2018; 53(6): 668–673.