Review
Copyright ©The Author(s) 2020.
World J Stem Cells. Apr 26, 2020; 12(4): 266-276
Published online Apr 26, 2020. doi: 10.4252/wjsc.v12.i4.266
Table 1 Expression of stem/progenitor immunophenotypes and genes of the intervertebral disc
Ref.Type of stem cellsExpression of stem cell/progenitor immunophenotypes and genes
Human
Liu et al[35], 2016NP-MSCsCD73+, CD90+, CD105+, Oct4+, Nanog+, Jagged+ and Notch1+, CD34-, CD45-,HLA-DR-
Li et al[36], 2017NP-SCsGD2+, Tie2+
Li et al[37], 2018NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-, HLA-DR-
Jia et al[38], 2017D-NP-MSCs/ND-NP-MSCsCD73+, CD90+, CD105+, Oct4+ and Nanog+, CD34-, CD45-, HLA-DR-
Wu et al[40], 2017NP-SCs/NPPCsCD29+, CD44+, CD 73+, CD90+, CD105+, Oct4+ and Nanog+, CD11b-, CD14-, CD34-, CD45-, HLA-DR-
Wang et al[41], 2016NP-SCs/AF-SCs/CEP-SCsCD73+, CD90+, CD105+, CD19-, CD34-, CD45-, HLA-DR-
Liang et al[42], 2018NP-MSCsCD73+, CD90+, CD105+, Sox2+ and Oct4+, CD14-, CD19-, CD34-, HLA-DR-
Daisuke et al[43], 2012NPPCsTie2+, GD2+
Chen et al[44], 2018NP-MSCsCD73+, CD90+, CD105+, CD34-, HLA-DR-
Quan et al[48], 2015NP-MSCsCD29+, CD44+, CD105+, CD14-, CD34-, CD45-, HLA-DR-
Liu et al[49], 2017AF-MSCs, NP-MSCs, CEP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-, HLA-DR-
Blanco et al[27], 2010NP-MSCsCD73+, CD90+, CD105+, CD106+, CD166+, CD19-, CD34-, CD45-, HLA-DR-
Lazzarini et al[50], 2018NP-MSCsCD13+, CD73+, CD90+, CD105+, CD11b-, CD14-, CD19-, CD45-, HLA-DR-
Pereira et al[51], 2016CEP-MSCsNot shown
Qi et al[57], 2018NP-MSCsCD24+, CD73+, CD90+, CD105+, CD29-, CD45-
Rat
Zhao et al[34], 2017NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-
Li et al[39], 2019NP-MSCsCD44+, CD73+, CD90+, CD105+, Oct4+, Nanog+ and Sox2+, CD34-, HLA-DR-
Li et al[45], 2013NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-
Wang et al[46], 2019NP-MSCsCD73+, CD90+, CD105, Tie2+, CD34-, CD45-
Nan et al[52], 2019NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-
Han et al[29], 2014NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-
Tao et al[28], 2013NP-MSCsCD73+, CD90+, CD105+, Nanog+, Sox2+, Rex1+ and Oct4+, CD34-, CD45-
Tao et al[53], 2015NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-
Liu et al[30], 2019N-NP-MSCs/D-NP-MSCsCD73+, CD90+, CD105+, CD166+, Sox2+, Nanog+, Oct4+, LIF+, PCNA+ and C-KIT+, CD34-, CD45-
Li et al[55], 2018NP-MSCsCD73+, CD90+, CD105+, CD34-, CD45-
Cheng et al[56], 2019NP-MSCsCD29+, CD44+, CD90+, CD34-, CD45-
Lin et al[58], 2017NP-MSCs/NPPCsCD29+, CD44+, CD90+, Nanog+, Oct4+ and Sox2+, CD34-, CD45-
Liu et al[68], 2019NP-MSCsCD73+, CD90+, CD105+, Sox2+, Nanog+ and Oct4+, CD34-, CD45-
Zhang et al[69], 2015NP-MSCsCD44+, CD73+, CD90+, CD105+, Sox2+, Nanog+ and Oct4+, CD14-, CD34-, CD45-, HLA-DR-
Dog
Erwin et al[47], 2013NPPCsOct3/4+, Sox2+, CD133+, Nanog+ and Nestin+
Bovine
Tekari et al[63], 2016NPPCsTie2+
Rabbit
Jia et al[54], 2018NP-MSCsCD29+, CD44+, CD166+, CD4-, CD8-, CD14-
MSC: Mesenchymal stem cell; NP: Nucleus pulposus; AF: Annulus fibrosus; CEP: Cartilaginous endplates; NPPC: NP-derived progenitor cell.
Table 2 Highlights and strategy of endogenous repair
Ref.Cells, biomaterial, and medicineHighlights and strategy
Human
Liu et al[35], 2016AmilorideThe biological behavior of NP-MSCs could be inhibited by acidic conditions, and amiloride may meliorate IVD degeneration by improving the activities of NP-MSCs.
Li et al[36], 2017NP-SCsNP-SCs keep the regeneration ability similar to BMSCs with superior capacity in chondrogenesis.
Li et al[37], 2018Modified notochordal cell-rich NP explantsModified notochordal cell-rich NP explants can attenuate degeneration and senescence of NP-MSC induced by TNF-α.
Jia et al[38], 2017D-NP-MSCs/ND-NP-MSCsD-NP-MSCs displayed decreased biological characteristics compared with NP-MSCs.
Wu et al[40], 2017D-NP-MSCs/UCMSCsD-NP-MSCs had lower expression of phenotype markers and exhibited reduced proliferation capability and differentiation potentials compared with UCMSCs.
Wang et al[41], 2016NPSCs/AFSCs/CESCsA comparison of the osteogenic capacities: CESCs > AFSCs > BM-MSCs > NPSCs; for adipogenesis: BM-MSCs > NPSCs > CESCs > AFSCs; in chondrogenesis: CESCs > AFSCs > BMSCs > NPSCs.
Liang et al[42], 2018NP-MSCsThe biological behavior of NP-MSCs could be inhibited by compression loading.
Daisuke et al[43], 2012NPPCsThe frequency of Tie2+ cells decreases markedly in tissue with age and degeneration of the IVD, suggesting exhaustion of their capacity for regeneration.
Chen et al[44], 2018ICAThe addition of ICA to the conventional freezing medium could improve the viability and function of cryopreserved human NP-MSCs.
Quan et al[48], 2015MSC-like cells from NPNP tissue contains MSC-like cells which could be isolated and proliferate in vitro.
Liu et al[49], 2017AF-MSCs, NP-MSCs, CEP-MSCsAF-MSCs, NP-MSCs, and CEP-MSCs showed similar multilineage differentiation abilities; CEP-MSCs have the most powerful properties of migration and invasion when compared with AF-MSCs and NP-MSCs.
Blanco et al[27], 2010NP-MSCsNP-MSCs were quite similar to BM-MSCs, with the exception that NP-MSCs are not able to differentiate into adipocytes.
Lazzarini et al[50], 2018NP-MSCsNP-MSCs have the capacity of neuronal differentiation and could express neural markers without any electric functional properties.
Pereira et al[51], 2016CEP-MSCsMSCs from CEP promote IVD regeneration by remodeling ECM.
Qi et al[57], 2018MSC-CMMSC-CM has potential to alleviate HG induced cell cycle arrest and ECM degradation of NP-MSCs via p38 MAPK pathway.
Li et al[64], 2018CsACsA efficiently inhibited compression-induced NP-MSCs apoptosis by alleviating mitochondrial dysfunction and oxidative stress.
Rat
Zhao et al[34], 2017NP-MSCsThe efficacy of NP-MSCs is compromised by age, and old NP-MSCs displayed senescent features.
Li et al[39], 2019NP-MSCsThe MSC-CM + CC method (MSC complete medium culture + cloning cylinder) is a more reliable and efficient way for isolating and purifying NP-MSCs.
Li et al[45], 2013NP-MSCsCompared to AD-MSCs, NP-MSCs showed greater viability, proliferation, and chondrocytic differentiation under hypoxia.
Wang et al[46], 2019Injectable hydrogel-loaded NP-MSCsInjectable hydrogel-loaded NP-MSCs transplantation can delay the level of IVD degeneration and promote the regeneration of the degenerative IVD in a rat model.
Nan et al[52], 2019NarNar efficiently attenuated H2O2-induced NP-MSCs apoptosis and mitochondrial dysfunction through PI3/AKT pathway.
Han et al[29], 2014NP-MSCsAn acidic environment is a major obstacle for IVD regeneration by AD-MSCs or NP-MSCs; NP-MSCs appeared less sensitive to inhibition by acidic PH.
Tao et al[28], 2013NPCs-NP-MSCs co-cultureNP-MSCs could tolerate IVD-like high osmolarity and NPCs-NP-MSCs co-culture increased cell proliferation and the expression of SOX-9, aggrecan, and collagen-II.
Tao et al[53], 2015TGF-β3/IGF-1The synergy between TGF-β3 and IGF-1 enhanced NP-MSCs viability, ECM biosynthesis, and differentiation towards NPCs by activating the MAPK/ERK signaling pathway.
Liu et al[30], 2019N-NP-MSCs/D-NP-MSCsN-NP-MSCs showed a significantly higher proliferation rate, better stemness maintenance ability, but reduced cell apoptosis rate compared with D-NP-MSCs.
Li et al[55], 2018NP-MSCsHyperosmolarity of the IVD significantly inhibited the proliferation and chondrogenic differentiation of NP-MSCs by activating the ERK pathway.
Cheng et al[56], 2019TNF-αTreatment with a high concentration of TNF-α (50-200 ng/mL) could induce apoptosis of NP-MSCs, whereas a relatively low TNF-α concentration (0.1-10 ng/mL) promoted the proliferation and migration of NP-MSCs, but inhibited their differentiation toward NP cells.
Lin et al[58], 2017L-PD of NP-MSCsNP-MSCs at a L-PD (5 cells/cm2) have better biological characteristic, stronger multilineage differentiation, and higher expression of stem cell biomarkers compared with those at an M-PD (100 cells/cm2) and H-PD (10000 cells/cm2).
Yang et al[65], 2009BMSCsBMSCs could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells.
Liu et al[68], 2019NP-MSCsHigh glucose concentration significantly decrease vitality, migration, and stemness of NP-MSCs.
Zhang et al[69], 2015NP-MSCsThe chondrogenic ability of NP-MSCs and BM-MSCs was similar under induction in vitro.
Dog
Erwin et al[47], 2013NPPCsNPPCs have higher expression of the Nanog gene compared to MSCs and are capable of differentiation along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo in the myelin-deficient shiverer mouse.
Bovine
Tekari et al[63], 2016NPPCsThe Tie2+ cells (NPPC) were spheroid in shape with capacity of multi-differentiation and may decline fast, which was partially reversed by FGF2 and hypoxic conditions.
Rabbit
Jia et al[54], 2018P-PRP/L-PRPBoth P-PRP and L-PRP could induce the proliferation and NP-differentiation of NP-MSCs; P-PRP could reduce the inflammatory and catabolic responses by avoiding the activation of the NF-κB pathway.
Rhesus macaque
Huang et al[66], 2013DPCs, SLRPSLRP could reduce the susceptibility of DPCs to hypoxia-induced apoptosis via promoting the activation/stabilization of HIF-1α and HIF-2α.
MSC: Mesenchymal stem cell; IVD: Intervertebral disc; NP: Nucleus pulposus; AF: Annulus fibrosus; CEP: Cartilaginous endplates; UCMSCs: Umbilical cord MSCs; AD: Adipose tissue; ECM: Extracellular matrix; ICA: Icariin; CM: Conditioned medium; HG: High glucose; CsA: Cyclosporine; Nar: Naringin; TGF-β3: Transforming growth factor beta 3; IGF: Insulin-like growth factor; TNF: Tumor necrosis factor; L-PD: Low plating density; NPPC: NP-derived progenitor cell; BM-MSC: Bone marrow mesenchymal stem cell; P-PRP: Pure platelet-rich plasma; L-PRP: Leukocyte-containing platelet-rich plasma; DPCs: Intervertebral disc progenitor cells; SLRP: Leucine-rich proteoglycans.