J. Kobolak, A. Dinnyes, A. Memic, A. Khademhosseini, and A. Mobasheri, Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche, Methods, vol.99, pp.62-68, 2016.

J. Liu, F. Yu, Y. Sun, B. Jiang, W. Zhang et al., Concise reviews: Characteristics and potential applications of human dental tissue-derived mesenchymal stem cells, Stem Cells Dayt, vol.33, pp.627-638, 2015.

F. Rastegar, D. Shenaq, J. Huang, W. Zhang, B. Zhang et al., Mesenchymal stem cells: Molecular characteristics and clinical applications, World J. Stem Cells, vol.2, pp.67-80, 2010.

M. J. Hoogduijn and E. Lombardo, Concise Review: Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era?, Stem Cells Transl. Med, vol.8, pp.1126-1134, 2019.

G. T. Huang, .. Sonoyama, W. Liu, Y. Liu, H. Wang et al., The hidden treasure in apical papilla: The potential role in pulp/dentin regeneration and bioroot engineering, J. Endod, vol.34, pp.645-651, 2008.

W. Sonoyama, Y. Liu, T. Yamaza, R. S. Tuan, S. Wang et al., Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study, J. Endod, vol.34, pp.166-171, 2008.

A. Bakopoulou and I. About, Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application, Stem Cells Int, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01454805

J. Kang, W. Fan, Q. Deng, H. He, and F. Huang, Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy, BioMed. Res. Int, p.6104738, 2019.

O. A. Nada and R. M. Backly, Stem Cells from the Apical Papilla (SCAP) as a Tool for Endogenous Tissue Regeneration, Front. Bioeng. Biotechnol, vol.6, 2018.

A. Leyendecker-junior, C. C. Gomes-pinheiro, T. Fernandes, and D. Franco-bueno, The use of human dental pulp stem cells for in vivo bone tissue engineering: A systematic review, J. Tissue Eng, vol.9, 2018.

W. L. Grayson, F. Zhao, B. Bunnell, and T. Ma, Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells, Biochem. Biophys. Res. Commun, vol.358, pp.948-953, 2007.

Z. Ivanovic, Hypoxia or in situ normoxia: The stem cell paradigm, J. Cell. Physiol, vol.219, pp.271-275, 2009.

Z. Ivanovic and M. Vlaski-lafarge, Harnessing anaerobic nature of stem cells for use in regenerative medicine, Anaerobiosis and Stemness: An Evolutionary Paradigm, pp.258-286, 2016.

C. Gorin, G. Y. Rochefort, R. Bascetin, H. Ying, J. Lesieur et al., Priming Dental Pulp Stem Cells with Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion, Stem Cells Transl. Med, vol.5, pp.392-404, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01622175

R. Shi, H. Yang, X. Lin, Y. Cao, C. Zhang et al., Analysis of the characteristics and expression profiles of coding and noncoding RNAs of human dental pulp stem cells in hypoxic conditions, Stem Cell Res. Ther, vol.10, 2019.

G. D'ippolito, S. Diabira, G. A. Howard, P. Menei, B. A. Roos et al., Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential, J. Cell Sci, vol.117, pp.2971-2981, 2004.

G. D'ippolito, S. Diabira, G. A. Howard, B. A. Roos, and P. C. Schiller, Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells, vol.39, pp.513-522, 2006.

C. Rios, G. Ippolito, K. M. Curtis, G. J. Delcroix, . .-r et al., Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells, Stem Cells Dev, vol.25, pp.848-860, 2016.

D. P. Lennon, J. M. Edmison, and A. I. Caplan, Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension: Effects on in vitro and in vivo osteochondrogenesis, J. Cell. Physiol, vol.187, pp.345-355, 2001.

H. Ren, Y. Cao, Q. Zhao, J. Li, C. Zhou et al., Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions, Biochem. Biophys. Res. Commun, vol.347, pp.12-21, 2006.

Z. Ivanovic and M. Vlaski-lafarge, In situ normoxia versus "Hypoxia, Anaerobiosis and Stemness: An Evolutionary Paradigm, pp.17-21, 2016.

R. Schäfer, G. Spohn, and P. C. Baer, Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?, Transfus. Med. Hemother, vol.43, pp.256-267, 2016.

J. R. Choi, B. Pingguan-murphy, W. A. Wan-abas, M. A. Noor-azmi, S. Z. Omar et al., Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells, Biochem. Biophys. Res. Commun, vol.448, pp.218-224, 2014.

C. Fotia, A. Massa, F. Boriani, N. Baldini, and D. Granchi, Prolonged exposure to hypoxic milieu improves the osteogenic potential of adipose derived stem cells, J. Cell. Biochem, vol.116, pp.1442-1453, 2015.

C. Mas-bargues, J. Sanz-ros, A. Román-domínguez, M. Inglés, L. Gimeno-mallench et al., Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine, Int. J. Mol. Sci, 1195.

P. Boya, P. Codogno, and N. Rodriguez-muela, Autophagy in stem cells: Repair, remodelling and metabolic reprogramming, Dev. Camb. Engl, vol.145, 2018.

A. J. Meijer and P. Codogno, Regulation and role of autophagy in mammalian cells, Int. J. Biochem. Cell Biol, vol.36, pp.2445-2462, 2004.

A. Sotthibundhu, W. Promjuntuek, M. Liu, S. Shen, and P. Noisa, Roles of autophagy in controlling stem cell identity: A perspective of self-renewal and differentiation, Cell Tissue Res, vol.374, pp.205-216, 2018.

J. Guan, A. K. Simon, M. Prescott, J. A. Menendez, F. Liu et al., Autophagy in stem cells, Autophagy, vol.9, pp.830-849, 2013.

I. Tanida, T. Ueno, and E. Kominami, LC3 conjugation system in mammalian autophagy, Int. J. Biochem. Cell Biol, vol.36, pp.2503-2518, 2004.

G. L. Semenza, Mitochondrial autophagy: Life and breath of the cell, Autophagy, vol.4, pp.534-536, 2008.

P. A. Ney, Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX, Biochim. Biophys. Acta, vol.1853, pp.2775-2783, 2015.

H. J. Lee, Y. H. Jung, G. E. Choi, S. H. Ko, S. Lee et al., BNIP3 induction by hypoxia stimulates FASN-dependent free fatty acid production enhancing therapeutic potential of umbilical cord blood-derived human mesenchymal stem cells, Redox Biol, vol.13, pp.426-443, 2017.

D. E. Martin, J. F. De-almeida, M. A. Henry, Z. Z. Khaing, C. E. Schmidt et al., Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation, J. Endod, vol.40, pp.51-55, 2014.

R. Devillard, M. Rémy, J. Kalisky, J. Bourget, O. Kérourédan et al., In vitro assessment of a collagen/alginate composite scaffold for regenerative endodontics, Int. Endod. J, vol.50, pp.48-57, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02617452

J. H. Campbell and G. R. Campbell, Culture techniques and their applications to studies of vascular smooth muscle, Clin. Sci, vol.85, pp.501-513, 1993.

S. K. Greenwood, R. B. Hill, J. T. Sun, M. J. Armstrong, T. E. Johnson et al., Population doubling: A simple and more accurate estimation of cell growth suppression in the in vitro assay for chromosomal aberrations that reduces irrelevant positive results, Environ. Mol. Mutagen, vol.43, pp.36-44, 2004.

D. Duval, M. Trouillas, C. Thibault, D. Dembele, F. Diemunsch et al., Apoptosis and differentiation commitment: Novel insights revealed by gene profiling studies in mouse embryonic stem cells, Cell Death Differ, vol.13, pp.564-575, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00187902

A. A. Hammoud, N. Kirstein, V. Mournetas, A. Darracq, S. Broc et al., Murine Embryonic Stem Cell Plasticity Is Regulated through Klf5 and Maintained by Metalloproteinase MMP1 and Hypoxia, PLoS ONE, vol.11, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-02870978

I. Smyrek and E. H. Stelzer, Quantitative three-dimensional evaluation of immunofluorescence staining for large whole mount spheroids with light sheet microscopy, Biomed. Opt. Express, vol.8, pp.484-499, 2017.

D. Coronado, M. Godet, P. Bourillot, Y. Tapponnier, A. Bernat et al., A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency, Stem Cell Res, vol.10, pp.118-131, 2013.

C. Elabd, T. E. Ichim, K. Miller, A. Anneling, V. Grinstein et al., Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome: Implication for stem cell therapies targeting intervertebral discs, J. Transl. Med, vol.16, 2018.

B. Antebi, L. A. Rodriguez, K. P. Walker, A. M. Asher, R. M. Kamucheka et al., Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells, Stem Cell Res. Ther, vol.9, 2018.

P. Aguilar and V. Lertchirakarn, Comparison of stem cell behaviors between indigenous high and low-CD24 percentage expressing cells of stem cells from apical papilla (SCAPs), Tissue Cell, vol.48, pp.397-406, 2016.

S. Wang, M. Mo, J. Wang, S. Sadia, B. Shi et al., Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property, Cell. Mol. Life Sci, vol.75, pp.547-561, 2018.

J. K. Henderson, J. S. Draper, H. S. Baillie, S. Fishel, J. A. Thomson et al., Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens, Stem Cells, vol.20, pp.329-337, 2002.

K. Yu, S. Yang, J. Jung, H. Kim, K. Ko et al., CD49f enhances multipotency and maintains stemness through the direct regulation of OCT4 and SOX2, Stem Cells Dayt, vol.30, pp.876-887, 2012.

R. Alvarez, H. Lee, C. Hong, and C. Wang, Single CD271 marker isolates mesenchymal stem cells from human dental pulp, Int. J. Oral Sci, vol.7, pp.205-212, 2015.

K. Takahashi, K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka et al., Induction of pluripotent stem cells from adult human fibroblasts by defined factors, Cell, vol.131, pp.861-872, 2007.

F. V. Sbrana, M. Cortini, S. Avnet, F. Perut, M. Columbaro et al., The Role of Autophagy in the Maintenance of Stemness and Differentiation of Mesenchymal Stem Cells, Stem Cell Rev, vol.12, pp.621-633, 2016.

G. Cossu, M. Birchall, T. Brown, P. De-coppi, E. Culme-seymour et al., Lancet Commission: Stem cells and regenerative medicine, Lancet, vol.391, pp.883-910, 2018.

M. G. Cipolleschi, E. Rovida, Z. Ivanovic, V. Praloran, M. Olivotto et al., The expansion of murine bone marrow cells preincubated in hypoxia as an in vitro indicator of their marrow-repopulating ability, Leukemia, vol.14, pp.735-739, 2000.

M. Hammoud, M. Vlaski, P. Duchez, J. Chevaleyre, X. Lafarge et al., Combination of low O 2 concentration and mesenchymal stromal cells during culture of cord blood CD34(+) cells improves the maintenance and proliferative capacity of hematopoietic stem cells, J. Cell. Physiol, vol.227, pp.2750-2758, 2012.

L. Leroux, B. Descamps, N. F. Tojais, B. Séguy, P. Oses et al., Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway, Mol. Ther. J. Am. Soc. Gene Ther, vol.18, pp.1545-1552, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00509086

C. Grau-monge, G. J. Delcroix, . .-r, A. Bonnin-marquez, M. Valdes et al., Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease, Biomed. Mater, vol.12, 2017.

C. Niculescu, G. Ganguli-indra, V. Pfister, V. Dupé, N. Messaddeq et al., Conditional ablation of integrin alpha-6 in mouse epidermis leads to skin fragility and inflammation, Eur. J. Cell Biol, vol.90, pp.270-277, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00532916

A. De-arcangelis, H. Hamade, F. Alpy, S. Normand, E. Bruyère et al., , vol.66, pp.1748-1760, 2017.

Z. Qiryaqoz, S. Timilsina, D. Czarnowski, P. H. Krebsbach, and L. G. Villa-diaz, Identification of biomarkers indicative of functional skeletal stem cells, Orthod. Craniofac. Res, vol.22, pp.192-198, 2019.

Z. Yang, P. Dong, X. Fu, Q. Li, S. Ma et al., CD49f Acts as an Inflammation Sensor to Regulate Differentiation, Adhesion, and Migration of Human Mesenchymal Stem Cells, Stem Cells Dayt, vol.33, pp.2798-2810, 2015.

H. Inoue, N. Nagata, H. Kurokawa, and S. Yamanaka, iPS cells: A game changer for future medicine, EMBO J, vol.33, pp.409-417, 2014.

K. Takahashi, K. Okita, M. Nakagawa, and S. Yamanaka, Induction of pluripotent stem cells from fibroblast cultures, Nat. Protoc, vol.2, pp.3081-3089, 2007.

G. Pattappa, S. D. Thorpe, N. C. Jegard, H. K. Heywood, J. D. De-bruijn et al., Continuous and uninterrupted oxygen tension influences the colony formation and oxidative metabolism of human mesenchymal stem cells, Tissue Eng. Part. C Methods, vol.19, pp.68-79, 2013.

M. Nawaz, F. Fatima, K. C. Vallabhaneni, P. Penfornis, H. Valadi et al., Extracellular Vesicles: Evolving Factors in Stem Cell Biology, Stem Cells Int, 2016.

G. L. Semenza, Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1, Annu. Rev. Cell Dev. Biol, vol.15, pp.551-578, 1999.

G. L. Semenza, Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology, Annu. Rev. Pathol, vol.9, pp.47-71, 2014.

X. Chen, Y. He, and F. Lu, Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation. Stem Cells Int, 2018.

F. Ma, R. Li, H. Tang, T. Zhu, F. Xu et al., Regulation of autophagy in mesenchymal stem cells modulates therapeutic effects on spinal cord injury, Brain Res, 2019.

L. Esteban-martínez and P. Boya, BNIP3L/NIX-dependent mitophagy regulates cell differentiation via metabolic reprogramming, Autophagy, vol.14, pp.915-917, 2017.

A. Singh, M. Azad, M. D. Shymko, E. S. Henson, S. Katyal et al., The BH3 only Bcl-2 family member BNIP3 regulates cellular proliferation, PLoS ONE, vol.13, 2018.

, This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, © 2019 by the authors. Licensee MDPI