Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2018

Open Access 01-12-2018 | Research article

Evaluation of bone marrow-derived mesenchymal stem cell quality from patients with congenital pseudoarthrosis of the tibia

Authors: Ismail Hadisoebroto Dilogo, Fajar Mujadid, Retno Wahyu Nurhayati, Aryadi Kurniawan

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2018

Login to get access

Abstract

Background

The treatment of congenital pseudoarthrosis of the tibia (CPT) remains challenging in pediatric orthopedics due to the difficulties in bone union, continuous angulation, joint stiffness, and severe limb length discrepancy. Mesenchymal stem cells (MSCs) therapy offers a complementary approach to improve the conventional surgical treatments. Although the autologous MSC treatment shows a promising strategy to promote bone healing in CPT patients, the quality of MSCs from CPT patients has not been well studied. The purpose of this study is to investigate the quality of MSCs isolated from patients with CPT.

Methods

The bone marrow-derived MSCs from the fracture site and iliac crest of six CPT patients were isolated and compared. The cumulative population doubling level (cPDL), phenotype characteristics, and trilineage differentiation potency were observed to assess the quality of both MSCs.

Results

There were no significant differences of the MSCs derived from the fracture site and the MSCs from the iliac crest of the subjects, in terms of cPDL, phenotype characteristics, and trilineage differentiation potency (all p > 0.05). However, MSCs from the fracture site had a higher senescence tendency than those from the iliac crest.

Conclusion

MSC quality is not the main reason for delayed bone regeneration in those with CPT. Thus, autologous MSC is a promising source for treating CPT patients
Literature
1.
go back to reference Hardinge K. Congenital anterior bowing of the tibia. The significance of the different types in relation to pseudarthrosis. Ann R Coll Surg Engl. 1972;51(1):17–30.PubMedPubMedCentral Hardinge K. Congenital anterior bowing of the tibia. The significance of the different types in relation to pseudarthrosis. Ann R Coll Surg Engl. 1972;51(1):17–30.PubMedPubMedCentral
2.
go back to reference Hefti F, Bollini G, Dungl P, Fixsen J, Grill F, Ippolito E, Romanus B, Tudisco C, Wientroub S. Congenital pseudarthrosis of the tibia: history, etiology, classification, and epidemiologic data. J Pediatr Orthop B. 2000;9:11–5.CrossRef Hefti F, Bollini G, Dungl P, Fixsen J, Grill F, Ippolito E, Romanus B, Tudisco C, Wientroub S. Congenital pseudarthrosis of the tibia: history, etiology, classification, and epidemiologic data. J Pediatr Orthop B. 2000;9:11–5.CrossRef
3.
go back to reference Andersen KS. Radiological classification of congenital pseudarthrosis of the tibia. Acta Orthop Scand. 1973;44(6):719–27.CrossRef Andersen KS. Radiological classification of congenital pseudarthrosis of the tibia. Acta Orthop Scand. 1973;44(6):719–27.CrossRef
4.
go back to reference DeClue JE, Cohen BD, Lowy DR. Identification and characterization of the neurofibromatosis type 1 protein product. P Natl Acad Sci USA. 1991;88:9914–8.CrossRef DeClue JE, Cohen BD, Lowy DR. Identification and characterization of the neurofibromatosis type 1 protein product. P Natl Acad Sci USA. 1991;88:9914–8.CrossRef
5.
go back to reference Abramowicz A, Gos M. Neurofibromin in neurofibromatosis type 1 mutations in NF1 gene as a cause of disease. Dev Period Med. 2014;18(3):297–306.PubMed Abramowicz A, Gos M. Neurofibromin in neurofibromatosis type 1 mutations in NF1 gene as a cause of disease. Dev Period Med. 2014;18(3):297–306.PubMed
6.
go back to reference Crawford AH, Schorry EK. Neurofibromatosis update. J Pediatr Orthop. 2006;26:413–23.CrossRef Crawford AH, Schorry EK. Neurofibromatosis update. J Pediatr Orthop. 2006;26:413–23.CrossRef
7.
go back to reference Pannier S. Congenital pseudarthrosis of the tibia. Orthop Traumatol-Sur. 2011;97:750–61.CrossRef Pannier S. Congenital pseudarthrosis of the tibia. Orthop Traumatol-Sur. 2011;97:750–61.CrossRef
8.
go back to reference Magnani M, Racano C, Abati C, Granchi D, Vescovi V, Stilli S. Use of MSC in the treatment of the congenital pseudoarthrosis in children. Surg Sci. 2014;5:555–61.CrossRef Magnani M, Racano C, Abati C, Granchi D, Vescovi V, Stilli S. Use of MSC in the treatment of the congenital pseudoarthrosis in children. Surg Sci. 2014;5:555–61.CrossRef
9.
go back to reference Tikkanen J, Leskelä HV, Lehtonen ST, Vähäsarja V, Melkko J, Ahvenjärvi L, Pääkkö E, Väänänen K, Lehenkari P. Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation. Cytotherapy. 2010;12(5):593–604.CrossRef Tikkanen J, Leskelä HV, Lehtonen ST, Vähäsarja V, Melkko J, Ahvenjärvi L, Pääkkö E, Väänänen K, Lehenkari P. Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation. Cytotherapy. 2010;12(5):593–604.CrossRef
10.
go back to reference Secunda R, Vennila R, Mohanashankar AM, Rajasundari M, Jeswanth S, Surendran R. Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study. Cytotechnology. 2015;67(5):793–807.CrossRef Secunda R, Vennila R, Mohanashankar AM, Rajasundari M, Jeswanth S, Surendran R. Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study. Cytotechnology. 2015;67(5):793–807.CrossRef
11.
go back to reference Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Dj P, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. Cytotherapy. 2006;8(4):315–7.CrossRef Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Dj P, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. Cytotherapy. 2006;8(4):315–7.CrossRef
12.
go back to reference Pawitan JA, Feroniasanti L, Kispa T, Dilogo IH, Fasha I, Kurniawati T, Liem IK. Simple method to isolate mesenchymal stem cells from bone marrow using xeno-free material: a preliminary study. Int J PharmTech Res. 2015;7(2):354–9. Pawitan JA, Feroniasanti L, Kispa T, Dilogo IH, Fasha I, Kurniawati T, Liem IK. Simple method to isolate mesenchymal stem cells from bone marrow using xeno-free material: a preliminary study. Int J PharmTech Res. 2015;7(2):354–9.
13.
go back to reference Ng CP, Sharif ARM, Health DE, Chow JW, Zhang CBY, Chan-Park MB, Hammond PT, Chan JKY, Griffith LG. Enhanced ex vivo expansion of adult mesenchymal stem cells by mesenchymal stem cell ECM. Biomaterials. 2014;35:4046–57.CrossRef Ng CP, Sharif ARM, Health DE, Chow JW, Zhang CBY, Chan-Park MB, Hammond PT, Chan JKY, Griffith LG. Enhanced ex vivo expansion of adult mesenchymal stem cells by mesenchymal stem cell ECM. Biomaterials. 2014;35:4046–57.CrossRef
14.
go back to reference Nobuhiro I, Lin LR, Reddy VN. Effect of growth factors on proliferation and differentiation in human lens epithelial cells in early subculture. Invest Opthal Vis Sci. 1995;36:2304–12. Nobuhiro I, Lin LR, Reddy VN. Effect of growth factors on proliferation and differentiation in human lens epithelial cells in early subculture. Invest Opthal Vis Sci. 1995;36:2304–12.
15.
go back to reference Shebaby W, Abdalla EK, Saad F, Faour WH. Data on isolating mesenchymal stromal cells from human adipose tissue using a collagenase-free method. Data Brief. 2016;6:974–9.CrossRef Shebaby W, Abdalla EK, Saad F, Faour WH. Data on isolating mesenchymal stromal cells from human adipose tissue using a collagenase-free method. Data Brief. 2016;6:974–9.CrossRef
16.
go back to reference Schneider CA, Rasband WS, Eliceiri KW. NIH image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.CrossRef Schneider CA, Rasband WS, Eliceiri KW. NIH image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.CrossRef
17.
go back to reference Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater. 2012;2012(23):13–27.CrossRef Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater. 2012;2012(23):13–27.CrossRef
18.
go back to reference Nora CCV, Camassola M, Bellagamba B, Ikuta N, Cristoff AP, Meirelles LS, Ayres R, Margis R, Nardi NB. Molecular analysis of the differentiation potential of murine mesenchymal stem cells from tissues of endodermal or mesodermal origin. Stem Cells Dev. 2012;21:1761–8.CrossRef Nora CCV, Camassola M, Bellagamba B, Ikuta N, Cristoff AP, Meirelles LS, Ayres R, Margis R, Nardi NB. Molecular analysis of the differentiation potential of murine mesenchymal stem cells from tissues of endodermal or mesodermal origin. Stem Cells Dev. 2012;21:1761–8.CrossRef
19.
go back to reference Granchi D, Devescovi V, Baglio SR, Magnani M, Donzelli O, Baldini N. A regenerative approach for bone repair in congenital pseudarthrosis of the tibia associated or not associated with type 1 neurofibromatosis: correlation between laboratory findings and clinical outcome. Cytotherapy. 2012;14(3):306–14.CrossRef Granchi D, Devescovi V, Baglio SR, Magnani M, Donzelli O, Baldini N. A regenerative approach for bone repair in congenital pseudarthrosis of the tibia associated or not associated with type 1 neurofibromatosis: correlation between laboratory findings and clinical outcome. Cytotherapy. 2012;14(3):306–14.CrossRef
20.
go back to reference Shah H, Rousset M, Canavese F. Congenital pseudoarthrosis of the tibia: management and complications. Indian J Orthop. 2012;46(6):616–26.CrossRef Shah H, Rousset M, Canavese F. Congenital pseudoarthrosis of the tibia: management and complications. Indian J Orthop. 2012;46(6):616–26.CrossRef
21.
go back to reference Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015;35(2).CrossRef Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015;35(2).CrossRef
22.
go back to reference Narbona-Carceles J, Vaquero J, Suárez-Sancho S, Forriol F, Fernández-Santos ME. Bone marrow mesenchymal stem cell aspirates from alternative sources: is the knee as good as the iliac crest? Injury. 2014;45(Suppl 4):S42–7.CrossRef Narbona-Carceles J, Vaquero J, Suárez-Sancho S, Forriol F, Fernández-Santos ME. Bone marrow mesenchymal stem cell aspirates from alternative sources: is the knee as good as the iliac crest? Injury. 2014;45(Suppl 4):S42–7.CrossRef
23.
go back to reference Ng CP, Sharif AR, Heath DE, Chow JW, Zhang CB, Chan-Park MB, Hammond PT, Chan JK, Griffith LG. Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal stem cell ECM. Biomaterials. 2014;35(13):4046–57.CrossRef Ng CP, Sharif AR, Heath DE, Chow JW, Zhang CB, Chan-Park MB, Hammond PT, Chan JK, Griffith LG. Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal stem cell ECM. Biomaterials. 2014;35(13):4046–57.CrossRef
24.
go back to reference Mark P, Kleinsorge M, Gaebel R, Lux CA, Toelk A, Pittermann E, David R, Steinhoff G, Ma N. Human mesenchymal stem cells display reduced expression of CD105 after culture in serum-free medium. Stem Cells Int. 2013;2013:698076.CrossRef Mark P, Kleinsorge M, Gaebel R, Lux CA, Toelk A, Pittermann E, David R, Steinhoff G, Ma N. Human mesenchymal stem cells display reduced expression of CD105 after culture in serum-free medium. Stem Cells Int. 2013;2013:698076.CrossRef
25.
go back to reference Cleary MA, Narcisi R, Focke K, van der Linden R, Brama PA, van Osch GJ. Expression of CD105 on expanded mesenchymal stem cells does not predict their chondrogenic potential. Osteoarthr Cartilage. 2016;24(5):868–72.CrossRef Cleary MA, Narcisi R, Focke K, van der Linden R, Brama PA, van Osch GJ. Expression of CD105 on expanded mesenchymal stem cells does not predict their chondrogenic potential. Osteoarthr Cartilage. 2016;24(5):868–72.CrossRef
26.
go back to reference Bajada S, Marshall MJ, Wright KT, Richardson JB, Johnson WE. Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells. Bone. 2009;45:726–35.CrossRef Bajada S, Marshall MJ, Wright KT, Richardson JB, Johnson WE. Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells. Bone. 2009;45:726–35.CrossRef
27.
go back to reference Diaz-Solano D, Wittig O, Motta JD, Cardier JE. Isolation and characterization of multipotential mesenchymal stromal cells from congenital pseudoarthrosis of the tibia: case report. Anat Rec. 2015;298:1804–14.CrossRef Diaz-Solano D, Wittig O, Motta JD, Cardier JE. Isolation and characterization of multipotential mesenchymal stromal cells from congenital pseudoarthrosis of the tibia: case report. Anat Rec. 2015;298:1804–14.CrossRef
Metadata
Title
Evaluation of bone marrow-derived mesenchymal stem cell quality from patients with congenital pseudoarthrosis of the tibia
Authors
Ismail Hadisoebroto Dilogo
Fajar Mujadid
Retno Wahyu Nurhayati
Aryadi Kurniawan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2018
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-018-0977-9

Other articles of this Issue 1/2018

Journal of Orthopaedic Surgery and Research 1/2018 Go to the issue