Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Frontiers of Materials Science

ISSN 2095-025X

ISSN 2095-0268(Online)

CN 11-5985/TB

Postal Subscription Code 80-974

2018 Impact Factor: 1.701

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Front. Mater. Sci.    2014, Vol. 8 Issue (1) : 32-38    https://doi.org/10.1007/s11706-014-0236-x
MINI-REVIEW
Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells
Jin-Ling MA1,2,*(),Jeroen J. J. P. van den BEUCKEN2,Ju-Li PAN1,3,Fu-Zhai CUI4,Su CHEN1,*()
1. Department of VIP Service, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
2. Department of Biomaterials, Radboudumc, Nijmegen, the Netherlands
3. Department of Oral and Maxillofacial Surgery, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
4. State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
 Download: PDF(120 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Cellular strategies remain a crucial component in bone tissue engineering (BTE). So far, the outcome of cell-based strategies from initial clinical trials is far behind compared to animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the tissue-engineered constructs. Cocultures, by introducing angiogenic cells into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, pre-clinical studies demonstrated that cocultures enhance vascularization and bone formation compared to monocultures. However, there has been no report on the application of cocultures in clinics. Therefore, this mini-review aims to provide an overview regarding (i) critical parameters in cocultures and the outcomes of cocultures compared to monocultures in the currently available pre-clinical studies using human mesenchymal stem cells implanted in orthotopic animal models; and (ii) the usage of monocultures in clinical application in BTE.
Keywords mesenchymal stem cell (MSC)      endothelial cell (EC)      coculture      vasculari-zation      tissue regeneration     
Corresponding Author(s): Jin-Ling MA   
Issue Date: 24 June 2014
 Cite this article:   
Jin-Ling MA,Jeroen J. J. P. van den BEUCKEN,Ju-Li PAN, et al. Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells[J]. Front. Mater. Sci., 2014, 8(1): 32-38.
 URL:  
https://academic.hep.com.cn/foms/EN/10.1007/s11706-014-0236-x
https://academic.hep.com.cn/foms/EN/Y2014/V8/I1/32
Cell sourcesScaffoldObservation timeRepair siteEfficacy of bone & vessel formation (percentage, coculture/monoculture)Ref.
BM-MSCs/ECsPLGA12 weeksRat calvariumBone percentage/%: 1.4 (vs. MSCs)Donor derived vessels percentage/%: 10.0 (vs. MSCs)[31]
BM-MSCs/EPCsβ-TCP8 weeksRat femurBone percentage/%: 1.2 (vs. MSCs)Vessel density/mm-2: 1.0 (vs. MSCs) or 2.7 (vs. EPCs)[32]
BM-MSCs/EPCsβ-TCP1 weekRat femurNew bone mass: 1.3 (vs. MSCs)Vessel density/mm-2: 7.1 (vs. MSCs) or 2.5 (vs. EPCs)[33]
BM-MSCs/ECsβ-TCP16 weeksRabbit ulnaBone percentage/%: 1.3 (vs. MSCs)Vessel percentage/%: 1.2 (vs. MSCs)[10]
AT-MSCs/ECsPCL/PLGA/β-TCP12 weeksRat calvariumBone percentage/%: 1.3 (vs. MSCs)[34]
AT-MSCs/ECsTi8 weeksRat calvariumBone percentage/%: 0.3 (vs. MSCs)[35]
Tab.1  Pre-clinical studies using human cell-based cocultures in BTE
Cell sourcesPatientsCurrent statusRepair sitesOutcome or purposeReference or ClinicalTrials.gov identifier
BM-MSCs1CompletedAlveolar boneRegenerated bone bridged the defect after 6 months.[39]
BM-MSCs2CompletedAlveolar boneThe integrity of the bone defects for the two patients are 34.5% and 25.6%.[40]
BM-MSCs54CompletedCraniofacial boneTo determine optimal culturing and transplantation conditions for the eventual transplantation of BM-MSCs into human recipients.NCT00001391
BM-MSCs6CompletedMandibleBone regeneration was observed in 50% (3/6) of the patients.[41]
BM-MSCs3CompletedMandibleBone healing was observed in 2 out of the 3 patients.[42]
BM-MSCs1CompletedMandibleSuccessful bone regeneration in the mandible.[43]
BM-MSCs7CompletedMaxillaThe mean percentage of the newly formed bone was 41%.[44]
BM-MSCs10Recruiting participants (from July 2011 on)MaxillaTo study the efficiency of BM-MSCs seeded in the autologous plasma matrix to repair the bone cysts in the maxillofacial region.NCT01389661
AT-MSCs1CompletedMaxillaThe new regenerated bone was mature 2 months after surgery.[45]
DP-MSCs17CompletedMandibleThe follow-up outcomes 1 year after surgery indicate that bone regeneration was complete.[46]
DP-MSCs5Recruiting participants (from May 2013 on)Alveolar boneTo analyze the bone forming capacity to reconstruct the alveolar bone defect in cleft lip and palate patients using DP-MSCs.NCT01932164
Tab.2  Clinical studies using human MSCs-based monocultures in BTE
ATadipose tissue
BMbone marrow
BTEbone tissue engineering
Cx43connexin 43
DPdental pulp
ECendothelial cell
EPCendothelial progenitor cell
HUVEChuman umbilical vein endothelial cell
MSCmesenchymal stem cell
OBosteoblast
PCLpolycaprolactone
PLGApoly lactic-co-glycolic acid
TCPβ-tricalcium phosphate
Tab.3  
1 ScherberichA, MüllerA M, SchäferD J, . Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. Journal of Cellular Physiology, 2010, 225(2): 348–353
2 MaJ, van den BeuckenJ J, YangF, . Coculture of osteoblasts and endothelial cells: optimization of culture medium and cell ratio. Tissue Engineering Part C: Methods, 2011, 17(3): 349–357
3 XueY, XingZ, HellemS, . Endothelial cells influence the osteogenic potential of bone marrow stromal cells. BioMedical Engineering Online, 2009, 8(1): 34
4 MeyerU W H. Bone and Cartilage Engineering. Berlin: Springer-Verlag/New York, LLC, 2006
5 PedersenT O, BloisA L, XueY, . Osteogenic stimulatory conditions enhance growth and maturation of endothelial cell microvascular networks in culture with mesenchymal stem cells. Journal of Tissue Engineering, 2012, 3(1): 2041731412443236
6 ZhaoX, LiuL, WangF K, . Coculture of vascular endothelial cells and adipose-derived stem cells as a source for bone engineering. Annals of Plastic Surgery, 2012, 69(1): 91–98
7 TrkovS, EngG, Di LiddoR, . Micropatterned three-dimensional hydrogel system to study human endothelial-mesenchymal stem cell interactions. Journal of Tissue Engineering and Regenerative Medicine, 2010, 4(3): 205–215
8 SantosM I, UngerR E, SousaR A, . Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone-starch scaffold and the in vitro development of vascularization. Biomaterials, 2009, 30(26): 4407–4415
9 TaoJ, SunY, WangQ G, . Induced endothelial cells enhance osteogenesis and vascularization of mesenchymal stem cells. Cells Tissues Organs, 2009, 190(4): 185–193
10 ZhouJ, LinH, FangT, . The repair of large segmental bone defects in the rabbit with vascularized tissue engineered bone. Biomaterials, 2010, 31(6): 1171–1179
11 KoobS, Torio-PadronN, StarkG B, . Bone formation and neovascularization mediated by mesenchymal stem cells and endothelial cells in critical-sized calvarial defects. Tissue Engineering Part A, 2011, 17(3–4): 311–321
12 GeuzeR E, WegmanF, ÖnerF C, . Influence of endothelial progenitor cells and platelet gel on tissue-engineered bone ectopically in goats. Tissue Engineering Part A, 2009, 15(11): 3669–3677
13 UngerR E, SartorisA, PetersK, . Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials. Biomaterials, 2007, 28(27): 3965–3976
14 HofmannA, RitzU, VerrierS, . The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds. Biomaterials, 2008, 29(31): 4217–4226
15 Thein-HanW, XuH H. Prevascularization of a gas-foaming macroporous calcium phosphate cement scaffold via coculture of human umbilical vein endothelial cells and osteoblasts. Tissue Engineering Part A, 2013, 19(15–16): 1675–1685
16 RouwkemaJ, WesterweelP E, de BoerJ, . The use of endothelial progenitor cells for prevascularized bone tissue engineering. Tissue Engineering Part A, 2009, 15(8): 2015–2027
17 PedersenT O, BloisA L, XueY, . Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation. Stem Cell Research & Therapy, 2014, 5: 23
18 SteffensL, WengerA, StarkG B, . In vivo engineering of a human vasculature for bone tissue engineering applications. Journal of Cellular and Molecular Medicine, 2009, 13(9b): 3380–3386
19 FuchsS, GhanaatiS, OrthC, . Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds. Biomaterials, 2009, 30(4): 526–534
20 GraingerS J, PutnamA J. Assessing the permeability of engineered capillary networks in a 3D culture. PLoS ONE, 2011, 6(7): e22086
21 SteinerD, LampertF, StarkG B, . Effects of endothelial cells on proliferation and survival of human mesenchymal stem cells and primary osteoblasts. Journal of Orthopaedic Research, 2012, 30(10): 1682–1689
22 BidarraS J, BarriasC C, BarbosaM A, . Phenotypic and proliferative modulation of human mesenchymal stem cells via crosstalk with endothelial cells. Stem Cell Research, 2011, 7(3): 186–197
23 SunH, QuZ, GuoY, . In vitro and in vivo effects of rat kidney vascular endothelial cells on osteogenesis of rat bone marrow mesenchymal stem cells growing on polylactide-glycoli acid (PLGA) scaffolds. BioMedical Engineering Online, 2007, 6(1): 41 (7 pages)
24 BulnheimU, MüllerP, NeumannH-G, . Endothelial cells stimulate osteogenic differentiation of mesenchymal stem cells on calcium phosphate scaffolds. Journal of Tissue Engineering and Regenerative Medicine, 2012, doi: 10.1002/term.1590
25 KangY, KimS, FahrenholtzM, . Osteogenic and angiogenic potentials of monocultured and co-cultured human-bone-marrow-derived mesenchymal stem cells and human-umbilical-vein endothelial cells on three-dimensional porous beta-tricalcium phosphate scaffold. Acta Biomaterialia, 2013, 9(1): 4906–4915
26 GotmanI, Ben-DavidD, UngerR E, . Mesenchymal stem cell proliferation and differentiation on load-bearing trabecular Nitinol scaffolds. Acta Biomaterialia, 2013, 9(9): 8440–8448
27 PangH, WuX H, FuS L, . Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction. International Orthopaedics, 2013, 37(4): 753–759
28 LinR Z, Melero-MartinJ M. Bioengineering human microvascular networks in immunodeficient mice. Journal of Visualized Experiments, 2011, (53): e3065
29 SunL, ParkerS T, SyojiD, . Direct-write assembly of 3D silk/hydroxyapatite scaffolds for bone co-cultures. Advanced Healthcare Materials, 2012, 1(6): 729–735
30 GuZ, XieH, LiL, . Application of strontium-doped calcium polyphosphate scaffold on angiogenesis for bone tissue engineering. Journal of Materials Science: Materials in Medicine, 2013, 24(5): 1251–1260
31 KaiglerD, KrebsbachP H, WangZ, . Transplanted endothelial cells enhance orthotopic bone regeneration. Journal of Dental Research, 2006, 85(7): 633–637
32 SeebachC, HenrichD, KählingC, . Endothelial progenitor cells and mesenchymal stem cells seeded onto β-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. Tissue Engineering Part A, 2010, 16(6): 1961–1970
33 HenrichD, SeebachC, KaehlingC, . Simultaneous cultivation of human endothelial-like differentiated precursor cells and human marrow stromal cells on β-tricalcium phosphate. Tissue Engineering Part C: Methods, 2009, 15(4): 551–560
34 KimJ Y, JinG Z, ParkI S, . Evaluation of solid free-form fabrication-based scaffolds seeded with osteoblasts and human umbilical vein endothelial cells for use in vivo osteogenesis. Tissue Engineering Part A, 2010, 16(7): 2229–2236
35 MaJ, BothS K, JiW, . Adipose tissue-derived MSCs as monocultures or cocultures with human umbilical vein endothelial cells: Performance in vitro and in rat cranial defects. Journal of Biomedical Materials Research Part A, 2013, doi: 10.1002/jbm.a.34775
36 HeX, DziakR, YuanX, . BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects. PLoS ONE, 2013, 8(4): e60473
37 LiG, WangX, CaoJ, . Coculture of peripheral blood CD34+ cell and mesenchymal stem cell sheets increase the formation of bone in calvarial critical-size defects in rabbits. The British Journal of Oral & Maxillofacial Surgery, 2014, 52(2): 134–139
38 LiuJ, LiuC, SunB, . Differentiation of rabbit bone mesenchymal stem cells into endothelial cells in vitro and promotion of defective bone regeneration in vivo. Cell Bioche-mistry and Biophysics, 2014, 68(3): 479–487
39 HibiH, YamadaY, UedaM, . Alveolar cleft osteoplasty using tissue-engineered osteogenic material. International Journal of Oral and Maxillofacial Surgery, 2006, 35(6): 551–555
40 BehniaH, KhojastehA, SoleimaniM, . Secondary repair of alveolar clefts using human mesenchymal stem cells. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 2009, 108(2): e1–e6
41 MeijerG J, de BruijnJ D, KooleR, . Cell based bone tissue engineering in jaw defects. Biomaterials, 2008, 29(21): 3053–3061
42 ZamiriB, ShahidiS, EslaminejadM B, . Reconstruction of human mandibular continuity defects with allogenic scaffold and autologous marrow mesenchymal stem cells. The Journal of Craniofacial Surgery, 2013, 24(4): 1292–1297
43 LeeJ, SungH M, JangJ D, . Successful reconstruction of 15-cm segmental defects by bone marrow stem cells and resected autogenous bone graft in central hemangioma. Journal of Oral and Maxillofacial Surgery, 2010, 68(1): 188–194
44 ShayestehY S, KhojastehA, SoleimaniM, . Sinus augmentation using human mesenchymal stem cells loaded into a β-tricalcium phosphate/hydroxyapatite scaffold. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 2008, 106(2): 203–209
45 MesimäkiK, LindroosB, TörnwallJ, . Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. International Journal of Oral and Maxillofacial Surgery, 2009, 38(3): 201–209
46 d’AquinoR, De RosaA, LanzaV, . Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. European Cells & Materials, 2009, 18: 75–83
47 NishiM, MatsumotoR, DongJ, . Engineered bone tissue associated with vascularization utilizing a rotating wall vessel bioreactor. Journal of Biomedical Materials Research Part A, 2013, 101A(2): 421–427
48 HongM, JoH, AnkenyR F, . Influence of mesenchymal stem cells on the response of endothelial cells to laminar flow and shear stress. Cells, Tissues, Organs, 2013, 198(4): 289–299
49 BarronM J, GoldmanJ, TsaiC J, . Perfusion flow enhances osteogenic gene expression and the infiltration of osteoblasts and endothelial cells into three-dimensional calcium phosphate scaffolds. International Journal of Biomaterials, 2012, 2012: 915620 (10 pages)
[1] BAI Lun, ZUO Bao-qi, GUAN Guo-ping, DAI Li-xing, CHEN Yong-zhen, ZHOU Zheng-yu, XU Jian-mei, WU Zhen-yu. On the growth morphous of capillaries and tissue in porous silk fibroin films[J]. Front. Mater. Sci., 2008, 2(3): 266-270.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed