Due to their immunosuppressive potential and ability to differentiate into multiple musculoskeletal cell lineages, mesenchymal stromal cells (MSCs) became popular in clinical trials for the treatment of musculoskeletal disorders. The aim of this study was to isolate and characterize native populations of MSCs from human cortical and cancellous bone from the posterior elements of the lumbar spine and determine what source of MSCs yields better quality and quantity of cells to be potentially used for spinal fusion repair. We were able to show that MSCs from trabecular and cortical spine had the typical MSC morphology and expression markers; the ability to differentiate in adipocyte, chondrocyte, or osteoblast but they did not have a consistent pattern in the expression of the specific differentiation lineage genes. Moreover, MSCs from both sites demonstrated an immune suppression profile suggesting that these cells may have a more promising success in applications related to immunomodulation more than exploring their ability to drive osteogenesis to prevent nonunion in spine fusion procedures.
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References
1.
KimDH, RhimR, LiL, MarthaJ, SwaimBH, BancoRJ, JenisJL and TromanhauserSG. (2009). Prospective study of iliac crest bone graft harvest site pain and morbidity. Spine J, 9,(11)::886–892.
2.
HearyRF, SchlenkRP, SacchieriTA, BaroneD and BroteaC. (2002). Persistent iliac crest donor site pain: independent outcome assessment. Neurosurgery, 50,(3)::510–516.
3.
DiederichsS, ShineKM and TuanRS. (2013). The promise and challenges of stem cell-based therapies for skeletal diseases: stem cell applications in skeletal medicine: potential, cell sources and characteristics, and challenges of clinical translation. Bioessays, 35,(3)::220–230.
4.
RothrauffBB and TuanRS. (2014). Cellular therapy in bone-tendon interface regeneration. Organogenesis, 10,(1)::13–28.
5.
Tuan RS. (2013). Regenerative medicine in 2012: the coming of age of musculoskeletal tissue engineering. Nat Rev Rheumatol, 9,(2)::74–76.
6.
ToquetJ, RohanizadehR, GuicheuxJ, CouillaudS, PassutiN, DaculsiG and HeymannD. (1999). Osteogenic potential in vitro of human bone marrow cells cultured on macroporous biphasic calcium phosphate ceramic. J Biomed Mater Res, 44,(1)::98–108.
7.
MinWK, BaeJS, ParkBC, JeonIO, JinHK, SonMJ, ParkEK and KimSY. (2010). Proliferation and osteoblastic differentiation of bone marrow stem cells: comparison of vertebral body and iliac crest. Eur Spine J, 19,(10)::1753–1760.
8.
WhangPG and WangJC. (2003). Bone graft substitutes for spinal fusion. Spine J, 3,(2)::155–165.
9.
AgarwalR, WilliamsK, UmscheidCA and WelchWC. (2009). Osteoinductive bone graft substitutes for lumbar fusion: a systematic review. J Neurosurg Spine, 11,(6)::729–740.
10.
AbdullahKG, SteinmetzMP, BenzelEC and MrozTE. (2011). The state of lumbar fusion extenders. Spine (Phila Pa 1976), 36,(20)::E1328–E1334.
11.
GaoX, UsasA, TangY, LuA, TanJ, SchneppendahlJ, KozemchakAM, WangB, CumminsJH, TuanRS and HuardJ. (2014). A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP. Biomaterials, 35,(25)::6859–6870.
12.
RappoldI, ZieglerBL, KöhlerI, MarchettoS, RosnetO, BirnbaumD, SimmonsPJ, ZannettinoAC, HillB, et al. (1997). Functional and phenotypic characterization of cord blood and bone marrow subsets expressing FLT3 (CD135) receptor tyrosine kinase. Blood, 90,(1)::111–125.
13.
SimmonsPJ, PrzepiorkaD, ThomasED and Torok-StorbB. (1987). Host origin of marrow stromal cells following allogeneic bone marrow transplantation. Nature, 328,(6129)::429–432.
14.
GuptaPK, ChullikanaA, ParakhR, DesaiS, DasA, GottipamulaS, KrishnamurthyS, AnthonyN, PherwaniA and MajumdarAS. (2013). A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia. J Transl Med, 11:143.
15.
BiancoP, RobeyPG and SimmonsPJ. (2008). Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell, 2,(4)::313–319.
16.
Barbanti BrodanoG, TerziS, TrombiL, GriffoniC, ValtieriM, BorianiS and MagliMC. (2013). Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties. Eur Spine J, 22,(Suppl 6)::S979–S984.
17.
Caplan AI. (2007). Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol, 213,(2)::341–347.
18.
JorgensenC, GordeladzeJ and NoelD. (2004). Tissue engineering through autologous mesenchymal stem cells. Curr Opin Biotechnol, 15,(5)::406–410.
19.
Barbanti BrodanoG, MazzoniE, TognonM, GriffoniC and ManfriniM. (2012). Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion. Eur Spine J, 21,(Suppl 1)::S3–S9.
20.
PneumaticosSG, TriantafyllopoulosGK, ChatziioannouS, BasdraEK and PapavassiliouAG. (2011). Biomolecular strategies of bone augmentation in spinal surgery. Trends Mol Med, 17,(4)::215–222.
21.
JaiswalN, HaynesworthSE, CaplanAI and BruderSP. (1997). Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem, 64,(2)::295–312.
22.
RisbudMV and SittingerM. (2002). Tissue engineering: advances in in vitro cartilage generation. Trends Biotechnol, 20,(8)::351–356.
23.
HanY, LiX, ZhangY, HanY, ChangF and DingJ. (2019). Mesenchymal stem cells for regenerative medicine. Cells, 8(8):88624.
24.
WrightA, Arthaud-DayML and WeissML. (2021). Therapeutic use of mesenchymal stromal cells: the need for inclusive characterization guidelines to accommodate all tissue sources and species. Front Cell Dev Biol, 9:632717
25.
PengL, JiaZ, YinX, ZhangX, LiuY, ChenP, MaK and ZhouC. (2008). Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue. Stem Cells Dev, 17,(4)::761–773.
26.
FriedensteinAJ, PetrakovaKV, KurolesovaAI and FrolovaGP. (1968). Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation, 6,(2)::230–247.
27.
AhmedTA and HinckeMT. (2014). Mesenchymal stem cell-based tissue engineering strategies for repair of articular cartilage. Histol Histopathol, 29,(6)::669–689.
28.
ChenW, LiuJ, ManuchehrabadiN, WeirMD, ZhuZ and XuHHK. (2013). Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects. Biomaterials, 34,(38)::9917–9925.
29.
AbbottS, MackayG, DurdM, SolomonS and ZylberbergC. (2014). Twenty years of the International Society for Cellular Therapies: the past, present and future of cellular therapy clinical development. Cytotherapy, 16,(4 Suppl)::S112–S119.
30.
KatzAJ, TholpadyA, TholpadySS, ShangH and OgleRC. (2005). Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells, 23,(3)::412–423.
31.
NakagamiH, MorishitaR, MaedaK, KikuchiY, OgiharaT and KanedaY.(2006). Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J Atheroscler Thromb, 13(2):77–81.
32.
De UgarteDA, MorizonoK, ElbarbaryA, AlfonsoZ, ZukPA, ZhuM, DragooJL, AshjianP, ThomasB, et al. (2003). Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs, 174,(3)::101–109.
33.
ZukPA, ZhuM, AshjianP, De UgarteDA, HuangJI, MizunoH, AlfonsoZC, FraserJK, BenhaimP and HedrickMH. (2002). Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell, 13,(12)::4279–4295.
34.
SchafflerA and BuchlerC. (2007). Concise review: adipose tissue-derived stromal cells—basic and clinical implications for novel cell-based therapies. Stem Cells, 25,(4)::818–827.
35.
AmosPJ, KapurSK, StaporPC, ShangH, BekiranovS, KhurgelM, RodeheaverGT, PeirceSM and KatzAJ. (2010). Human adipose-derived stromal cells accelerate diabetic wound healing: impact of cell formulation and delivery. Tissue Eng Part A, 16,(A)::1595–1606.
36.
LiaoHT and ChenCT. (2014). Osteogenic potential: comparison between bone marrow and adipose-derived mesenchymal stem cells. World J Stem Cells, 6,(3)::288–295
37.
ShortBJ, BrouardN and SimmonsPJ. (2009). Prospective isolation of mesenchymal stem cells from mouse compact bone. Methods Mol Biol, 482:259–268.
38.
ZhuH, GuoZH, JiangXX, LiH, WangXY, YaoHY, ZhangY and MaoN. (2010). A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. Nat Protoc, 5,(3)::550–560.
39.
TuliR, SeghatoleslamiMR, TuliS, WangML, HozackJW, MannerPA, DanielsonKG and TuanetRS. (2003). A simple, high-yield method for obtaining multipotential mesenchymal progenitor cells from trabecular bone. Mol Biotechnol, 23,(1)::37–49.
40.
TuliR, TuliS, NandiS, WangML, AlexanderPG, Haleem-SmithH, HozackWJ, MannerPA, DanielsonKG and TuanRS. (2003). Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone. Stem Cells, 21,(6)::681–693.
41.
SakaguchiY, SekiyaI, YagishitaK, IchinoseS, ShinomiyaK and MunetaT. (2004). Suspended cells from trabecular bone by collagenase digestion become virtually identical to mesenchymal stem cells obtained from marrow aspirates. Blood, 104,(9)::2728–2735.
42.
QiaoS, RenH, ShiY and LiuW. (2014). Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism. Chin Med J (Engl), 127,(3)::475–482.
43.
SottileV, HalleuxC, BassilanaF, KellerH and SeuwenK. (2002). Stem cell characteristics of human trabecular bone-derived cells. Bone, 30,(5)::699–704.
44.
AhrensN, TorminA, PaulusM, RoostermanD, SalamaA, KrennV, NeumannU and SchedingS. (2004). Mesenchymal stem cell content of human vertebral bone marrow. Transplantation, 78,(6)::925–929.
45.
McLainRF, FlemingJE, BoehmCA and MuschlerGF. (2005). Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest. J Bone Joint Surg Am, 87,(12)::2655–2661.
46.
RisbudMV, ShapiroIM, GuttapalliA, Di MartinoA, DanielsonKG, BeinerMJ, HillibrandA, AlbertTG, AndersonDG and VaccaroRA. (2006). Osteogenic potential of adult human stem cells of the lumbar vertebral body and the iliac crest. Spine (Phila Pa 1976), 31,(1)::83–89.
47.
CorradettiB, TaraballiF, PowellS, SungD, MinardiS, FerrariM, WeinerBK and TasciottiE. (2015). Osteoprogenitor cells from bone marrow and cortical bone: understanding how the environment affects their fate. Stem Cells Dev, 24,(9)::1112–1123.
48.
Lange-ConsiglioA, TassanS, CorradettiB, MeucciA, PeregoR, BizzaroD and CremonesiF. (2013). Investigating the efficacy of amnion-derived compared with bone marrow-derived mesenchymal stromal cells in equine tendon and ligament injuries. Cytotherapy, 15,(8)::1011–1020.
49.
CorradettiB, CorreaniA, RomaldiniA, MariniMG, BizzaroD, PerriniC, CremonesiF and Lange-ConsiglioA. (2014). Amniotic membrane-derived mesenchymal cells and their conditioned media: potential candidates for uterine regenerative therapy in the horse. PLoS One, 9(10):e111324.
50.
AkpancarS, TatarO, TurgutH, AkyildizF and EkinciS. (2016). The current perspectives of stem cell therapy in orthopedic surgery. Arch Trauma Res, 5(4):e37976.
51.
SonntagVK and MarcianoFF. (1995). Is fusion indicated for lumbar spinal disorders?. Spine (Phila Pa 1976), 20,(24 Suppl)::138S–142S.
52.
BuserZ, BrodkeDS, YoussefJA, MeiselHJ, MyhreSL, HashimotoR, ParkJB, YoonST and WangJC. (2016). Synthetic bone graft versus autograft or allograft for spinal fusion: a systematic review. J Neurosurg Spine, 25,(4)::509–516.
53.
DimarJR, GlassmanSD, BurkusKJ and CarreonLY. (2006). Clinical outcomes and fusion success at 2 years of single-level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft. Spine (Phila Pa 1976), 31,(22)::2534–2539; discussion 2540.
54.
Epstein NE. (2006). A preliminary study of the efficacy of Beta Tricalcium Phosphate as a bone expander for instrumented posterolateral lumbar fusions. J Spinal Disord Tech, 19,(6)::424–429.
55.
SenguptaDK, TruumeesE, PatelCK, KazmierczakC, HughesB, EldersG and HerkowitzHN. (2006). Outcome of local bone versus autogenous iliac crest bone graft in the instrumented posterolateral fusion of the lumbar spine. Spine (Phila Pa 1976), 31,(9)::985–991.
56.
CorradettiB, MeucciA, BizzaroD, CremonesiF and Lange ConsiglioA. (2013). Mesenchymal stem cells from amnion and amniotic fluid in the bovine. Reproduction, 145,(4)::391–400.
57.
WangY, ZhaoL and HantashBM. (2010). Support of human adipose-derived mesenchymal stem cell multipotency by a poloxamer-octapeptide hybrid hydrogel. Biomaterials, 31,(19)::5122–5130.
58.
LovatiAB, CorradettiB, CremonesiF, BizzaroD and ConsiglioAL. (2012). Tenogenic differentiation of equine mesenchymal progenitor cells under indirect co-culture. Int J Artif Organs, 35,(11)::996–1005.
59.
Gutierrez-AguirreCH, Gómez-De-LeónA, Alatorre-RicardoJ, Cantú-RodríguezOG, González-LlanoO, Jaime-PérezJC, Mancías-GuerraC, Flores-JiménezJA and Gómez-AlmaguerD. (2014). Allogeneic peripheral blood stem cell transplantation using reduced-intensity conditioning in an outpatient setting in ABO-incompatible patients: are survival and graft-versus-host disease different?. Transfusion, 54,(5)::1269–1277.
60.
BongsoA and LeeEH. (2005). Stem cells: their definition, classification and sources. Stem Cells pp. 1–13.
61.
RiekstinaU, MucenieceR, CakstinaI, MuiznieksI and AncansJ. (2008). Characterization of human skin-derived mesenchymal stem cell proliferation rate in different growth conditions. Cytotechnology, 58,(3)::153–162.
62.
TuckerBA, KaramsadkarSS, KhanWS and PastidesP. (2010). The role of bone marrow derived mesenchymal stem cells in sports injuries. J Stem Cells, 5,(4)::155–166.
63.
StriogaM, ViswanathanS, DarinskasA, SlabyO and MichalekJ. (2012). Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev, 21(14):2724–2752.
64.
Fernandez-MoureJS, CorradettiB, ChanP, Van EpsJL, JanecekT, RameshwarP, WeinerBK and TasciottiE. (2015). Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis. Stem Cell Res Ther, 6:203.
65.
VeriterS, AndréW, AouassarN, PoirelHA, LafosseA, DocquierPL and DufraneD. (2015). Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: safety and Feasibility in Different “Hospital Exemption” Clinical Applications. PLoS One, 10(10):e0139566.
66.
SteinertAF, RackwitzL, GilbertF, NothU and TuanRS. (2012). Concise review: the clinical application of mesenchymal stem cells for musculoskeletal regeneration: current status and perspectives. Stem Cells Transl Med, 1,(3)::237–247.
67.
Fernandez-BancesI, Perez-BasterrecheaM, Perez-LopezS, BatallaDN, Fernandez RodriguezMA, Alvarez-ViejoM, Ferrero-GutierrezA, Menendez-MenendezY, Garcia-GalaJM, et al. (2013). Repair of long-bone pseudoarthrosis with autologous bone marrow mononuclear cells combined with allogenic bone graft. Cytotherapy, 15,(5)::571–577.
68.
FontesP, RaoAS, RicordiC, RybkaWB, DodsonFS, BroznickB, LuL, ZeeviA, ThomsonAW and VaskoC. (1994). Human bone marrow obtained from vertebral bodies: cell isolation, phenotyping, progenitor assay, and transplantation. Transpl Proceed, 26,(6)::3406–3407.
69.
MansillaE, MártireK, RoqueG, TauJM, MarínGH, CastumaMV, OrlandiG and TardittiA. (2013). Salvage of cadaver stem cells (CSCs) as a routine procedure: history or future for regenerative medicine. J Transplant Technols Res, 3:1.
70.
KangJ, AnH, HilibrandA, YoonST, KavanaghE and BodenS. (2012). Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine (Phila Pa 1976), 37,(12)::1083–1091.
71.
KruytMC, van GaalenSM, OnerFC, VerboutAJ, de BruijnJD and DhertWJA. (2004). Bone tissue engineering and spinal fusion: the potential of hybrid constructs by combining osteoprogenitor cells and scaffolds. Biomaterials, 25,(9)::1463–1473.
72.
NiuCC, TsaiTT, FuTS, LaiPL, ChenLH and ChenWJ. (2009). A comparison of posterolateral lumbar fusion comparing autograft, autogenous laminectomy bone with bone marrow aspirate, and calcium sulphate with bone marrow aspirate: a prospective randomized study. Spine (Phila Pa 1976), 34,(25)::2715–2719.
73.
DaiLY and JiangLS. (2008). Single-level instrumented posterolateral fusion of lumbar spine with beta-tricalcium phosphate versus autograft: a prospective, randomized study with 3-year follow-up. Spine (Phila Pa 1976), 33,(12)::1299–1304.
74.
Epstein NE. (2008). An analysis of noninstrumented posterolateral lumbar fusions performed in predominantly geriatric patients using lamina autograft and beta tricalcium phosphate. Spine J, 8,(6)::882–887.
75.
Dal PozzoS, UrbaniS, MazzantiB, LucianiP, DeleddaC, LombardiniL, BenvenutiS, PeriA, BosiA and SaccardiR. (2010). High recovery of mesenchymal progenitor cells with non-density gradient separation of human bone marrow. Cytotherapy, 12,(5)::579–586.
76.
CarrancioS, López-HolgadoN, Sánchez-GuijoFM, VillarónE, BarbadoV, TaberaS, Díez-CampeloM, BlancoJ, San MiguelJF and Del CañizoMC. (2008). Optimization of mesenchymal stem cell expansion procedures by cell separation and culture conditions modification. Exp Hematol, 36,(8)::1014–1021.
77.
FragkakisEM, El-JawhariJJ, DunsmuirRA, MillnerPA, RaoSA, HenshawKT, PountosI, JonesE and GiannoudisPV. (2018). Vertebral body versus iliac crest bone marrow as a source of multipotential stromal cells: comparison of processing techniques, tri-lineage differentiation and application on a scaffold for spine fusion. PLoS One, 13(5):e0197969.
78.
DefinoHL, da Silva HerreroCFP, CrippaGE, Sverzut BellesiniL, BelotiMM and RosaAL. (2009). In vitro proliferation and osteoblastic phenotype expression of cells derived from human vertebral lamina and iliac crest. Spine (Phila Pa 1976), 34,(15)::1549–1553.
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