Top

European Spine Journal

Published in:

01-11-2015 | Original Article

The presence of stem cells in potential stem cell niches of the intervertebral disc region: an in vitro study on rats

Authors: Rui Shi, Feng Wang, Xin Hong, Yun-Tao Wang, Jun-Ping Bao, Feng Cai, Xiao-Tao Wu

Published in: European Spine Journal | Issue 11/2015

Abstract

Purpose

The potential of stem cell niches (SCNs) in the intervertebral disc (IVD) region, which may be of great significance in the regeneration process, was recently proposed. To the best of our knowledge, no previous in vitro study has examined the characteristics of stem cells derived from the potential SCN of IVD (ISN). Therefore, increasing knowledge on ISN-derived stem cells (ISN-SCs) may provide a greater understanding of IVD degeneration and regeneration processes. We aimed to demonstrate the existence of ISN-SCs and to compare their characteristics with bone marrow mesenchymal stem cells (BMSCs) in vitro.

Methods

Sprague–Dawley rats (male, 10-week-old) were used in this study. ISN tissues were separated by ophthalmic surgical instruments under a dissecting microscope according to the anatomical areas. BMSCs and cells isolated from the ISN tissues were cultured and expanded in vitro. Passage 4 populations were used for further analysis with respect to colony-forming ability, cellular immunophenotype, cell cycle, stem cell-related gene expression, and proliferation and multipotential differentiation capacities.

Results

In general, both of ISN-SCs and mesenchymal stromal cells (MSCs) met the minimal criteria for the definition of multipotent mesenchymal stromal cells, including adherence to plastic, specific surface antigen expression, and multipotent differentiation potential. Especially, ISN-SCs even showed greater potential of osteogenesis and chondrogenesis. The ISN-SCs also expressed stem cell-related genes that were comparable to those of BMSCs, and had colony-forming and self-renewal abilities.

Conclusions

To the best of our knowledge, this is the first in vitro study aimed towards determining the existence and characteristics of ISN-SCs, which belong to the MSC family and with greater osteogenic and chondrogenic abilities than BMSCs according to our data. This finding may be of great significance for additional studies that investigate the migration of ISN-SCs into the IVD, and may provide a new perspective on different biological approaches for IVD self-regeneration.

Luo X, Pietrobon R, Sun SX, Liu GG, Hey L (2004) Estimates and patterns of direct health care expenditures among individuals with back pain in the United States. Spine (Phila Pa 1976) 29(1):79–86. doi:10.1097/01.BRS.0000105527.13866.0F CrossRef

Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A (2000) Low back pain in relation to lumbar disc degeneration. Spine (Phila Pa 1976) 25(4):487–492CrossRef

Wang H, Zhou Y, Huang B, Liu LT, Liu MH, Wang J, Li CQ, Zhang ZF, Chu TW, Xiong CJ (2014) Utilization of stem cells in alginate for nucleus pulposus tissue engineering. Tissue Eng Part A 20(5–6):908–920. doi:10.1089/ten.TEA.2012.0703 CrossRefPubMed

Clarke LE, Richardson SM, Hoyland JA (2015) Harnessing the potential of mesenchymal stem cells for IVD regeneration. Curr Stem Cell Res Ther 10(4):296–306CrossRefPubMed

Longo UG, Papapietro N, Petrillo S, Franceschetti E, Maffulli N, Denaro V (2012) Mesenchymal stem cell for prevention and management of intervertebral disc degeneration. Stem Cells Int 2012:921053. doi:10.1155/2012/921053 PubMedCentralPubMed

Cai F, Wu XT, Xie XH, Wang F, Hong X, Zhuang SY, Zhu L, Rui YF, Shi R (2015) Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits. Int Orthop 39(1):149–159. doi:10.1007/s00264-014-2481-0 CrossRefPubMed

Hoogendoorn RJW, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI, Helder MN (2008) Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med 12(6a):2205–2216. doi:10.1111/j.1582-4934.2008.00291.x PubMedCentralCrossRefPubMed

Song K, Gu T, Shuang F, Tang J, Ren D, Qin J, Hou S (2015) Adipose-derived stem cells improve the viability of nucleus pulposus cells in degenerated intervertebral discs. Mol Med Reports. doi:10.3892/mmr.2015.3895

Schofield R (1978) The relationship between the spleen colony-forming cell and the haematopoietic stem cell. Blood cells 4(1–2):7–25PubMed

10.

Jedrzejas M, Skowron K, Czekaj P (2012) Stem cell niches exposed to tobacco smoke. Przegl Lek 69(10):1063–1073PubMed

11.

Voog J, Jones DL (2010) Stem cells and the niche: a dynamic duo. Cell Stem Cell 6(2):103–115. doi:10.1016/j.stem.2010.01.011 PubMedCentralCrossRefPubMed

12.

Wang K, Zhao X, Kuang C, Qian D, Wang H, Jiang H, Deng M, Huang L (2012) Overexpression of SDF-1alpha enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. PLoS ONE 7(9):e43922. doi:10.1371/journal.pone.0043922 PubMedCentralCrossRefPubMed

13.

Christie KJ, Turnley AM (2012) Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain. Front Cell Neurosci 6:70. doi:10.3389/fncel.2012.00070 PubMedCentralCrossRefPubMed

14.

Madhavan L, Collier TJ (2010) A synergistic approach for neural repair: cell transplantation and induction of endogenous precursor cell activity. Neuropharmacology 58(6):835–844. doi:10.1016/j.neuropharm.2009.10.005 CrossRefPubMed

15.

Saha B, Jaber M, Gaillard A (2012) Potentials of endogenous neural stem cells in cortical repair. Front Cell Neurosci 6:14. doi:10.3389/fncel.2012.00014 PubMedCentralPubMed

16.

Yu H, Vu TH, Cho KS, Guo C, Chen DF (2014) Mobilizing endogenous stem cells for retinal repair. Transl Res 163(4):387–398. doi:10.1016/j.trsl.2013.11.011 PubMedCentralCrossRefPubMed

17.

Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KS, Yamamura K, Masuda K, Okano H, Ando K, Mochida J (2012) Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun 3:1264. doi:10.1038/ncomms2226 PubMedCentralCrossRefPubMed

18.

Liu LT, Huang B, Li CQ, Zhuang Y, Wang J, Zhou Y (2011) Characteristics of stem cells derived from the degenerated human intervertebral disc cartilage endplate. PLoS ONE 6(10):e26285. doi:10.1371/journal.pone.0026285 PubMedCentralCrossRefPubMed

19.

Huang B, Liu LT, Li CQ, Zhuang Y, Luo G, Hu SY, Zhou Y (2012) Study to determine the presence of progenitor cells in the degenerated human cartilage endplates. Eur Spine J 21(4):613–622. doi:10.1007/s00586-011-2039-4 PubMedCentralCrossRefPubMed

20.

Liu C, Guo Q, Li J, Wang S, Wang Y, Li B, Yang H (2014) Identification of rabbit annulus fibrosus-derived stem cells. PLoS ONE 9(9):e108239. doi:10.1371/journal.pone.0108239 PubMedCentralCrossRefPubMed

21.

Henriksson H, Thornemo M, Karlsson C, Hagg O, Junevik K, Lindahl A, Brisby H (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine (Phila Pa 1976) 34(21):2278–2287. doi:10.1097/BRS.0b013e3181a95ad2 CrossRef

22.

Henriksson HB, Lindahl A, Skioldebrand E, Junevik K, Tangemo C, Mattsson J, Brisby H (2013) Similar cellular migration patterns from niches in intervertebral disc and in knee-joint regions detected by in situ labeling: an experimental study in the New Zealand white rabbit. Stem Cell Res Therapy 4(5):104. doi:10.1186/scrt315 CrossRef

23.

Henriksson HB, Svala E, Skioldebrand E, Lindahl A, Brisby H (2012) Support of concept that migrating progenitor cells from stem cell niches contribute to normal regeneration of the adult mammal intervertebral disc: a descriptive study in the New Zealand white rabbit. Spine (Phila Pa 1976) 37(9):722–732. doi:10.1097/BRS.0b013e318231c2f7 CrossRef

24.

Sasaki N, Henriksson HB, Runesson E, Larsson K, Sekiguchi M, Kikuchi S, Konno S, Rydevik B, Brisby H (2012) Physical exercise affects cell proliferation in lumbar intervertebral disc regions in rats. Spine (Phila Pa 1976) 37(17):1440–1447. doi:10.1097/BRS.0b013e31824ff87d CrossRef

25.

Ishii Y, Thomas AO, Guo XE, Hung CT, Chen FH (2006) Localization and distribution of cartilage oligomeric matrix protein in the rat intervertebral disc. Spine (Phila Pa 1976) 31(14):1539–1546. doi:10.1097/01.brs.0000221994.61882.4a CrossRef

26.

Liang CZ, Li H, Tao YQ, Peng LH, Gao JQ, Wu JJ, Li FC, Hua JM, Chen QX (2013) Dual release of dexamethasone and transforming growth factor beta3 from polymeric microspheres for the stem cell matrix accumulation in a rat disc degeneration model. Acta Biomater. doi:10.1016/j.actbio.2013.08.019 PubMedCentral

27.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. doi:10.1080/14653240600855905 CrossRefPubMed

28.

Boxall SA, Jones E (2012) Markers for characterization of bone marrow multipotential stromal cells. Stem Cells Int 2012:975871. doi:10.1155/2012/975871 PubMedCentralCrossRefPubMed

29.

Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I (2007) Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 327(3):449–462. doi:10.1007/s00441-006-0308-z CrossRefPubMed

30.

Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119(2):203–210CrossRefPubMed

31.

Postacchini F, Bellocci M, Massobrio M (1984) Morphologic changes in annulus fibrosus during aging. An ultrastructural study in rats. Spine (Phila Pa 1976) 9(6):596–603CrossRef

32.

Sakaguchi Y, Sekiya I, Yagishita K, Muneta T (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 52(8):2521–2529. doi:10.1002/art.21212 CrossRefPubMed

33.

Karaoz E, Aksoy A, Ayhan S, Sariboyaci AE, Kaymaz F, Kasap M (2009) Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol 132(5):533–546. doi:10.1007/s00418-009-0629-6 CrossRefPubMed

34.

Lotfy A, Salama M, Zahran F, Jones E, Badawy A, Sobh M (2014) Characterization of mesenchymal stem cells derived from rat bone marrow and adipose tissue: a comparative study. Int J Stem Cells 7(2):135–142. doi:10.15283/ijsc.2014.7.2.135 PubMedCentralCrossRefPubMed

35.

Barzilay R, Sadan O, Melamed E, Offen D (2009) Comparative characterization of bone marrow-derived mesenchymal stromal cells from four different rat strains. Cytotherapy 11(4):435–442. doi:10.1080/14653240902849796 CrossRefPubMed

36.

Rebelatto CK, Aguiar AM, Moretao MP, Senegaglia AC, Hansen P, Barchiki F, Oliveira J, Martins J, Kuligovski C, Mansur F, Christofis A, Amaral VF, Brofman PS, Goldenberg S, Nakao LS, Correa A (2008) Dissimilar differentiation of mesenchymal stem cells from bone marrow, umbilical cord blood, and adipose tissue. Exp Biol Med (Maywood) 233(7):901–913. doi:10.3181/0712-RM-356 CrossRef

37.

Zhu H, Mitsuhashi N, Klein A, Barsky LW, Weinberg K, Barr ML, Demetriou A, Wu GD (2006) The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells 24(4):928–935. doi:10.1634/stemcells.2005-0186 CrossRefPubMed

38.

Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, Ratajczak MZ, Janowska-Wieczorek A (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 24(5):1254–1264. doi:10.1634/stemcells.2005-0271 CrossRefPubMed

39.

Xu X, Zhu F, Zhang M, Zeng D, Luo D, Liu G, Cui W, Wang S, Guo W, Xing W, Liang H, Li L, Fu X, Jiang J, Huang H (2013) Stromal cell-derived factor-1 enhances wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area and promoting neovascularization. Cells Tissues Organs 197(2):103–113. doi:10.1159/000342921 CrossRefPubMed

40.

Mayer H, Bertram H, Lindenmaier W, Korff T, Weber H, Weich H (2005) Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: autocrine and paracrine role on osteoblastic and endothelial differentiation. J Cell Biochem 95(4):827–839. doi:10.1002/jcb.20462 CrossRefPubMed

41.

Reems JA, Torok-Storb B (1995) Cell cycle and functional differences between CD34⁺/CD38hi and CD34⁺/38lo human marrow cells after in vitro cytokine exposure. Blood 85(6):1480–1487PubMed

42.

Jaenisch R, Young R (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132(4):567–582. doi:10.1016/j.cell.2008.01.015 PubMedCentralCrossRefPubMed

43.

Carlin R, Davis D, Weiss M, Schultz B, Troyer D (2006) Expression of early transcription factors Oct-4, Sox-2 and Nanog by porcine umbilical cord (PUC) matrix cells. Reprod Biol Endocrinol 4:8. doi:10.1186/1477-7827-4-8 PubMedCentralCrossRefPubMed

44.

Izadpanah R, Joswig T, Tsien F, Dufour J, Kirijan JC, Bunnell BA (2005) Characterization of multipotent mesenchymal stem cells from the bone marrow of rhesus macaques. Stem Cells Dev 14(4):440–451. doi:10.1089/scd.2005.14.440 CrossRefPubMed

45.

Silva J, Nichols J, Theunissen TW, Guo G, van Oosten AL, Barrandon O, Wray J, Yamanaka S, Chambers I, Smith A (2009) Nanog is the gateway to the pluripotent ground state. Cell 138(4):722–737. doi:10.1016/j.cell.2009.07.039 PubMedCentralCrossRefPubMed

46.

Boyle M, Wong C, Rocha M, Jones DL (2007) Decline in self-renewal factors contributes to aging of the stem cell niche in the drosophila testis. Cell Stem Cell 1(4):470–478. doi:10.1016/j.stem.2007.08.002 CrossRefPubMed

47.

Carlson ME, Conboy IM (2007) Loss of stem cell regenerative capacity within aged niches. Aging Cell 6(3):371–382. doi:10.1111/j.1474-9726.2007.00286.x PubMedCentralCrossRefPubMed

48.

Gopinath SD, Rando TA (2008) Stem cell review series: aging of the skeletal muscle stem cell niche. Aging Cell 7(4):590–598. doi:10.1111/j.1474-9726.2008.00399.x CrossRefPubMed

49.

Hunter CJ, Matyas JR, Duncan NA (2004) Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat 205(5):357–362. doi:10.1111/j.0021-8782.2004.00352.x PubMedCentralCrossRefPubMed

Title: The presence of stem cells in potential stem cell niches of the intervertebral disc region: an in vitro study on rats
Authors: Rui Shi
Feng Wang
Xin Hong
Yun-Tao Wang
Jun-Ping Bao
Feng Cai
Xiao-Tao Wu
Publication date: 01-11-2015
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 11/2015
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-015-4168-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The presence of stem cells in potential stem cell niches of the intervertebral disc region: an in vitro study on rats

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2015

The combined use of unilateral pedicle screw and contralateral facet joint screw fixation in transforaminal lumbar interbody fusion

Clinical and radiographic outcomes of concentrated bone marrow aspirate with allograft and demineralized bone matrix for posterolateral and interbody lumbar fusion in elderly patients

Screw augmentation for spinopelvic fixation in neuromuscular spine deformities: technical note

Restoration of lumbopelvic sagittal alignment and its maintenance following transforaminal lumbar interbody fusion (TLIF): comparison between straight type versus curvilinear type cage

Duration-dependent influence of dynamic torsion on the intervertebral disc: an intact disc organ culture study

Decision-making and patient’s expectations