PDF herunterladen
CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2017; 53(02): 104-120
DOI: 10.1055/s-0040-1712752
Original Article

Mechanisms of Action of Human Mesenchymal Stem Cells in Tissue Repair Regeneration and their Implications

Manisha Singh
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
,
Suchi Gupta
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
,
Sonali Rawat
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
,
Swati Midha
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
,
Krishan Gopal Jain
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
,
Manu Dalela
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
,
Sujata Mohanty
Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi
› Institutsangaben
› Weitere Informationen
  als PDF herunterladen Lizenzen und Reprints

ABSTRACT

Cell replacement therapy holds a promising future in the treatment of degenerative diseases related to neuronal, cardiac and bone tissues. In such kind of diseases, there is a progressive loss of specific types of cells. Currently the most upcoming and trusted cell candidate is Mesenchymal Stem Cells (MSCs) as these cells are easy to isolate from the tissue, easy to maintain and expand and no ethical concerns are linked. MSCs can be obtained from a number of sources like bone marrow, umbilical cord blood, umbilical cord, dental pulp, adipose tissues, etc. MSCs help in tissue repair and regeneration by various mechanisms of action like cell differentiation, immunomodulation, paracrine effect, etc. The future of regenerative medicine lies in tissue engineering and exploiting various properties to yield maximum output. In the current review article, we have targeted the repair and regeneration mechanisms of MSCs in neurodegenerative diseases, cardiac diseases and those related to bones. Yet there is a lot to understand, discover and then understand again about the molecular mechanisms of MSCs and then applying this knowledge in developing the therapy to get maximum repair and regeneration of concerned tissue and in turn the recovery of the patient.

Keywords

Differentiation - immunomodulation - exosomes - tissue engineering


Publikationsverlauf

Artikel online veröffentlicht:
09. Mai 2020

© .

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Friedenstein AJ, Piatetzky S II, Petrakova KV (1966). Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16: 381-390.
  • 2 Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968). Heterotopic of bone marrow: analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6: 230-247.
  • 3 Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970). The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3: 393-403.
  • 4 Friedenstein AJ, Deriglasova UF, Kulagina NN, et al (1974). Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 2: 83-92.
  • 5 Friedenstein AJ, Chailakhyan RK, Gerasimov UV (1987). Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 20: 263-272.
  • 6 Howlett CR, Cave J, Williamson M, et al (1986). Mineralization in in vitro cultures of rabbit marrow stromal cells. Clin Orthop Relat Res 213: 251-263.
  • 7 Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME (1992). Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci 102: 341-351.
  • 8 Rickard DJ, Sullivan TA, Shenker BJ, Leboy PS, Kazhdan I (1994). Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. Dev Biol 161: 218-228.
  • 9 Cheng SL, Yang JW, Rifas L, Zhang SF, Avioli LV (1994). Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology 134: 277-286.
  • 10 Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998). In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238: 265-272.
  • 11 Mackay AM, Beck SC, Murphy JM, et al (1998). Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng 4: 415-428.
  • 12 Lanotte M, Scott D, Dexter TM, Allen TD (1982). Clonal preadipocyte cell lines with different phenotypes derived from murine marrow stroma: factors influencing growth and adipogenesis in vitro. J Cell Physiol 111: 177-186.
  • 13 Wakitani S, Saito T, Caplan AI (1995). Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18: 14171426.
  • 14 Dominici M, Le Blanc K, Mueller I, et al (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8 (4): 315–317.
  • 15 Aggarwal S, Pittenger MF (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105: 1815–1822.
  • 16 Griffin MD, Elliman SJ, Cahill E, English K, Ceredig R, Ritter T (2013). Concise review: adult mesenchymal stromal cell therapy for inflammatory diseases: how well are we joining the dots? Stem Cells 31(10):2033–2041.
  • 17 Cutler AJ, Limbani V, Girdlestone J, Navarrete CV (2010). Umbilical cord-derived mesenchymal stromal cells modulate monocyte function to suppress Tcell proliferation. J Immunol 185(11):6617–6623.
  • 18 Ding DC, Chou HL, Chang YH, Hung WT, Liu HW, Chu TY (2016). Characterization of HLA -G and related immunosuppressive effects in human umbilical cord stroma- derived stem cells. Cell Transplant 25(2):217-228.
  • 19 Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF (2013). Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 34(6): 747-754.
  • 20 Yeo RY, Lai RC, Tan KH, Lim SK (2013). Exosome: A novel and safer therapeutic refinement of mesenchymal stem. J Circulating Biomarkers 1:1-12.
  • 21 Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164: 247-256.
  • 22 Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000). Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61: 364- 370.
  • 23 Suon S, Yang M, Iacovitti L (2006). Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson's disease. Brain Res 1106: 46-51.
  • 24 Kan I, Ben-Zur T, Barhum Y, et al (2007).Dopaminergic differentiation of human mesenchymal stem cells-utilization of bioassay for tyrosine hydroxylase expression. Neurosci Lett 419: 28-33.
  • 25 Barzilay R, Kan I, Ben-Zur T, et al (2008).Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols. Stem Cells Dev 17: 547-554.
  • 26 Tio M, Tan KH, Lee W, Wang TT, Udolph G (2010). Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells. PLoS ONE 5(2), e9398.
  • 27 Kim JH, Auerbach JM, Rodriguez-Gomez JA, et al (2002). Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418: 50-56.
  • 28 Jiang Y, Henderson D, Blackstad M, et al (2003). Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proc Natl Acad Sci USA 100: 11854-11860.
  • 29 Khoo ML, Tao H, Meedeniya AC, Mackay -Sim A, Ma DD (2011). Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents. PLoS ONE 6: e19025.
  • 30 Nandy SB, Mohanty S, Singh M, Behari M, Airan B (2014). Fibroblast Growth Factor-2 alone as an efficient inducer for differentiation of human bone marrow mesenchymal stem cells into dopaminergic neurons. J Biomed Sci 21:83.
  • 31 Zhang Z, Wang X, Wang S (2008). Isolation and characterization of mesenchymal stem cells derived from bone marrow of patients with Parkinson's disease. In Vitro Cell Dev Biol Anim 44: 169-177.
  • 32 Trzaska KA, Kuzhikandathil EV, Rameshwar P (2007). Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. Stem Cells 25: 2797-2808.
  • 33 Fu YS, Cheng YC, Lin MY, et al (2006).Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24: 115-124.
  • 34 Petschnik AE, Fell B, Tiede S, et al (2011). A novel xenogeneic co-culture system to examine neuronal differentiation capability of various adult human stem cells. PLoS ONE 6(9): e24944.
  • 35 Kim SS, Yoo SW, Park TS, et al (2008).Neural induction with neurogenin I increases the therapeutic effects of mesenchymal stem cells in the ischemic brain. Stem Cells 26: 2217-2228.
  • 36 Trzaska KA, Reddy BY, Munoz JL, Li KY, Ye JH, Rameshwar P (2008). Loss of RE1 silencing factor in mesenchymal cell derived dopamine progenitors induces functional maturity. Mol Cell Neurosci 39: 285-290.
  • 37 Wernig M, Zhao JP, Pruszak J, et al (2008).Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci (USA) 105(15): 5856-5861.
  • 38 Hu BY, Weick JP, Yu J, et al (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci (USA): 107(9): 4335-4340.
  • 39 Yim EK, Pang SW, Leong KW (2007). Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp Cell Res 313(9): 1820-1829.
  • 40 Carlberg B, Axell MZ, Nannmark U, Liu J, Kuhn HG (2009). Electrospun polyurethane scaffolds for proliferation and neuronal differentiation of human embryonic stem cells. Biomed Mater 4(4): 045004.
  • 41 Gardin C, Vindigni V, Bressan E, et al (2011). Hyaluronan and fibrin biomaterial as scaffolds for neuronal differentiation of adult stem cells derived from adipose tissue and skin. Int J Mol Sci 12: 67496763.
  • 42 Yang LY, Liu XM, Sun B, Hui GZ, Fei J, Guo LH (2004). Adipose tissue-derived stromal cells express neuronal phenotypes. Chin Med J (Engl) 117(3):425-429.
  • 43 Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G (2007). Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol 207(2):267-274.
  • 44 Ning H, Lin G, Fandel T, Banie L, Lue TF, Lin CS (2008). Insulin growth factor signaling mediates neuron -like differentiation of adipose-tissue-derived stem cells. Differentiation 76(5):488-494.
  • 45 Safford KM, Hicok KC, Safford SD, et al (2002). Neurogenic differentiation of murine and human adipose derived stromal cells. Biochem Biophys Res Commun 294(2):371-379.
  • 46 Safford KM, Safford SD, Gimble JM, Shetty AK, Rice HE (2004). Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells. Exp Neurol 187(2):319-328.
  • 47 Croft AP, Przyborski SA (2006). Formation of neurons by non-neural adult stem cells: potential mechanism implicates an artifact of growth in culture. Stem Cells 24(8):1841-1851.
  • 48 Xiong N, Zhang Z, Huang J, et al (2011). VEGF expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's Disease. Gene Ther 18: 394-402.
  • 49 Aanismaa R, Hautala J, Vuorinen A, Miettinen S, Narkilahti S (2012). Human dental pulp stem cells differentiate into neural precursors but not into mature functional neurons. Stem Cell Discovery 2(3): 85-91.
  • 50 Lee S-H, Lumelsky N, Studer L, Auerbach JM, McKay RD (2000). Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nature Biotechnol 18: 675-679.
  • 51 Raake P, von Degenfeld G, Hinkel R, et al (2004). Myocardial gene transfer by selective pressure-regulated retrofusion of coronary veins: comparison with surgical and percutaneous intramyocardial gene delivery. J Am Coll Cardiol 44:1124-1129.
  • 52 Kaur K, Yang J, Eisenberg CA, Eisenberg LM (2014). 5-azacytidine promotes the transdifferentiation of cardiac cells to skeletal myocytes. Cell Reprogram 16:324-330.
  • 53 Koyanagi M, Brandes RP, Haendeler J, Zeiher AM, Dimmeler S (2005). Cell-tocell connection of endothelial progenitor cells with cardiac myocytes by nanotubes: a novel mechanism for cell fate changes? Circ Res 96:1039-1041.
  • 54 Cselenyak A, Pankotai E, Horváth EM, Kiss L, Lacza Z (2010). Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections. BMC Cell Biology 11:29.
  • 55 Yong SK, Ahn Y, Kwon JS, et al (2012). Priming of mesenchymal stem cells with oxytocin enhances the cardiac repair in ischemia/reperfusion injury. Cells Tissues Organs 195:428-442.
  • 56 Mohanty S, Bose S, Jain KG, et al (2013). TGF-β1 contributes to cardiomyogeniclike differentiation of human bone marrow mesenchymal stem cells. Int J Cardiol 163:93-99.
  • 57 Kakkar A, Mohanty S, Bhargava B, Airan B (2015). Role of human cardiac biopsy derived conditioned media in modulating bone marrow derived mesenchymal stem cells toward cardiomyocyte-like cells. J Pract Cardiovasc Sci 1:150-155.
  • 58 He XQ, Chen MS, Li SH, et al (2010). Coculture with cardiomyocytes enhanced the myogenic conversion of mesenchymal stromal cells in a dose-dependent manner. Mol Cell Biochem 339: 89-98.
  • 59 Plotnikov EY, Khryapenkova TG, Vasileva AK, et al (2008). Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in co-culture. J Cell Mol Med 12:1622-1631.
  • 60 Berry MF, Engler AJ, Woo YJ, et al (2006). Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol 290: H2196-H2203.
  • 61 Makkar RR, Smith RR, Cheng K, et al (2012). Intracoronary cardiospherederived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379:895-904.
  • 62 Petrakova KV, Tolmacheva AA, Fridenshtein A (1963). Bone formation occurring in bone marrow transplantation in diffusion chambers. Biull Eksp Biol Med 56:87-91.
  • 63 Rawadi G, Vayssiere B, Dunn F, Baron R, Roman-Roman S (2003). BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. J Bone Miner Res 18:1842-1853.
  • 64 Cheng H, Jiang W, Phillips FM, et al (2003). Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 85:1544-1552.
  • 65 Spinella-Jaegle S, Roman-Roman S, Faucheu C, et al (2001). Opposite effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on osteoblast differentiation. Bone 29:323
  • 66 de Jong DS, van Zoelen EJ, Bauerschmidt S, Olijve W, Steegenga WT (2002). Microarray analysis of bone morphogenetic protein, transforming growth factor beta, and activin early response genes during osteoblastic cell differentiation. J Bone Miner Res 17:2119-2129.
  • 67 Taguchi Y, Yamamoto M, Yamate T, et al (1998). Interleukin-6-type cytokines stimulate mesenchymal progenitor differentiation toward the osteoblastic lineage. Proc Assoc Am Physicians 110:559-574.
  • 68 Kroger H, Soppi E, Loveridge N (1997). Growth hormone, osteoblasts, and marrow adipocytes: a case report. Calcif Tissue Int 61:33-35.
  • 69 Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL (1999). Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630-1638.
  • 70 Maeda S, Nobukuni T, Shimo-Onoda K, et al (2002). Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization. J Cell Physiol 193:73-79.
  • 71 Nurminskaya M, Magee C, Faverman L, Linsenmayer TF (2003). Chondrocytederived transglutaminase promotes maturation of preosteoblasts in periosteal bone. Dev Bio 263:139-152.
  • 72 Sottile V, Thomson A, McWhir J (2003). In vitro osteogenic differentiation of human ES cells. Cloning Stem Cells 5:149-155.
  • 73 Gupta A, Leong DT, Bai HF, Singh SB, Lim TC, Hutmacher DW (2007). Osteomaturation of adipose-derived stem cells required the combined action of vitamin D3, beta-glycerophosphate, and ascorbic acid. Biochem Biophys Res Commun 362:17-24.
  • 74 Zur Nieden NI, Kempka G, Ahr HJ (2003). In vitro differentiation of embryonic stem cells into mineralized osteoblasts. Differentiation 71:18-27.
  • 75 Raisz LG, Pilbeam CC, Fall PM (1993). Prostaglandins: mechanisms of action and regulation of production in bone. Osteoporos Int 3(Suppl 1):136-140.
  • 76 Weinreb M, Grosskopf A, Shir N (1999). The anabolic effect of PGE2 in rat bone marrow cultures is mediated via the EP4 receptor subtype. Am J Physiol 276:E376E383.
  • 77 Van Leeuwen JP, van Driel M, van den Bemd GJ, Pols HA (2001). Vitamin D control of osteoblast function and bone extracellular matrix mineralization. Crit Rev Eukaryot Gene Expr 11:199-226.
  • 78 Notoya K, Nagai H, Oda T, et al (1999). Enhancement of osteogenesis in vitro and in vivo by a novel osteoblast differentiation promoting compound, TAK-778. J Pharmacol Exp Ther 290:1054-1064.
  • 79 Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S (2000). Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun 271:688-692.
  • 80 Phillips BW, Belmonte N, Vernochet C, Ailhaud G, Dani C (2001). Compactin enhances osteogenesis in murine embryonic stem cells. Biochem Biophys Res Commun 284:478-484.
  • 81 Yourek G, McCormick SM, Mao JJ, Reilly GC (2010). Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen Med 5(5):713-724.
  • 82 Jansen JH, van der Jagt OP, Punt BJ, et al (2010). Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study. BMC Musculoskelet Disord 11:188-199.
  • 83 Hess R, Douglas T, Myers KA, et al (2010). Hydrostatic pressure stimulation of human mesenchymal stem cells seeded on collagen-based artificial extracellular matrices. J Biomech Eng 132(2):1-6.
  • 84 Lee KS, Kim HJ, Li QL, et al (2000). Runx2 is a common target of transforming growth factor beta 1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol 20(23):87838792.
  • 85 Lee MH, Kim YJ, Kim HJ, et al (2003). BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-β1 opposes the BMP-2 -induced osteoblast differentiation by suppression of Dlx5 expression. J Biol Chem 278(36):3438734394.
  • 86 Matsubara T, Kida K, Yamaguchi A, et al (2008). BMP2 regulates osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem 283(43):29119-29125.
  • 87 Harada S, Rodan GA (2003). Control of osteoblast function and regulation of bone mass. Nature 423(6937):349-355.
  • 88 Zippel N, Limbach CA, Ratajski N, et al (2012). Purinergic receptors influence the differentiation of human mesenchymal stem cells. Stem Cells Dev 21(6):884-900.
  • 89 Komori T (2006). Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99(5):1233-1239.
  • 90 Liu W, Toyosawa S, Furuichi T, et al (2001). Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 155(1):157-166.
  • 91 Nakashima K, Zhou X, Kunkel G, et al (2002). The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108(1): 17-29.
  • 92 Aubin JE, Liu F (1996). The osteoblast lineage. In: Principles of Bone Biology. Bilezikian JP, Raisz LG, Rodan GA, eds. San Diego, California, USA: Academic Press, 51-67.
  • 93 Pavlin D, Dove SB, Zadro R, Gluhak-Heinrich J (2000). Mechanical loading stimulates differentiation of periodontal osteoblasts in a mouse osteoinduction model: effect on type I collagen and alkaline phosphatase genes. Calcif Tissue Int 67(2):163-172.
  • 94 Pavlin D, Zadro R, Gluhak-Heinrich J (2001). Temporal pattern of stimulation of osteoblast-associated genes during mechanically-induced osteogenesis in vivo: early responses of osteocalcin and type I collagen. Connect Tissue Res 42(2):135-148.
  • 95 Aggarwal S, Pittenger MF (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815-1822.
  • 96 Ilancheran S, Moodley Y, Manuelpillai U (2009). Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta 30(1):2-10.
  • 97 Gonzalez-Hernandez A, LeMaoult J, Lopez A, et al (2005). Linking two immuno -suppressive molecules: indoleamine 2,3 dioxygenase can modify HLA-G cell-surface expression. Biol Reprod 73: 571–578.
  • 98 Nasef A, Mazurier C, Bouchet S, et al (2008). Leukemia inhibitory factor: role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol 253: 16-22.
  • 99 Ding DC, Chou HL, Chang YH, Hung WT, Liu HW, Chu TY (2016). Characterization of HLA -G and related immunosuppressive effects in human umbilical cord stroma-derived stem cells. Cell Transplant 25: 217-218.
  • 100 Griffin MD, Elliman SJ, Cahill E, English K, Ceredig R, Ritter T (2013). Concise review: adult mesenchymal stromal cell therapy for inflammatory diseases: how well are we joining the dots? Stem Cells 31(10):2033–2041.
  • 101 Cutler AJ, Limbani V, Girdlestone J, Navarrete CV (2010). Umbilical cord-derived mesenchymal stromal cells modulate monocyte function to suppress T cell proliferation. J Immunol 185(11):6617–6623.
  • 102 Hsuan YC, Lin CH, Chang CP, Lin MT (2016). Mesenchymal stem cell-based treatments for stroke, neural trauma, and heat stroke. Brain Behav 6(10): e00526.
  • 103 Patel DM, Shah J, Srivastava AS (2013). Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int 2013: Article ID 496218, 15 pages.
  • 104 Hu G, Drescher KM, Chen XM (2012). Exosomal miRNAs: biological properties and therapeutic potential. Front Genet 3:56.
  • 105 Yu B, Zhang X, Li X (2014). Exosomes derived from mesenchymal stem cells. Int J Mol Sci 15:4142–4157.
  • 106 Katsuda T, Tsuchiya R, Kosaka N, et al (2013). Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep 3: 1197.
  • 107 Seong JM, Kim BC, Park JH, Kwon IK, Mantalaris A, Hwang YS (2010). Stem cells in bone tissue engineering. Biomed Mater 5(6): 062001.
  • 108 Wang P, Liu X, Zhao L, et al (2015). Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium. Acta Biomaterialia 18: 236–248.
  • 109 109. Shao J, Zhang W, Yang T (2015). Using mesenchymal stem cells as a therapy for bone regeneration and repairing. Biol Res 48:62.
  • 110 Wu Q, Yang B, Hu K, Cao C, Man Y, Wang P (2017). Deriving osteogenic cells from induced pluripotent stem cells for bone tissue engineering. Tissue Eng Part B Rev 23(1): 1-8.
  • 111 Zhu W, Wang D, Xiong J, et al (2015). Study on clinical application of nanohydroxyapatite bone in bone defect repair. Artif Cells Nanomed Biotechnol 43(6): 361–365.
  • 112 Gao P, Zhang H, Liu Y, et al (2016). Betatricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo. Sci Rep 6:23367.
  • 113 Midha S, Kim TB, van den Bergh W, Lee PD, Jones JR, Mitchell CA (2013). Preconditioned 70S30C bioactive glass foams promote osteogenesis in vivo. Acta Biomater 9(11): 9169–9182.
  • 114 Kong L, Gao Y, Cao W, Gong Y, Zhao N, Zhang X (2005). Preparation and characterization of nanohydroxyapatite/chitosan composite scaffolds. J Biomed Mater Res A 75(2): 275–282.
  • 115 Jain KG, Singh M, Kakkar A, et al (2017). Evaluating the osteogenic potential of CHT/HAP/PCL biocomposites in bone tissue engineering: an in vivo study. Int J Sci Res 6(5): 10–13.
  • 116 Huang X, Bai S, Lu Q, Liu X, Liu S, Zhu H (2015). Osteoinductive-nanoscaled silk/HA composite scaffolds for bone tissue engineering application. J Biomed Mater Res B Appl Biomater 103(7): 1402–1414.
  • 117 Sun L, Parker ST, Syoji D, Wang X, Lewis JA, Kaplan DL (2012). Direct-write assembly of 3D silk/hydroxyapatite scaffolds for bone co-cultures. Adv Healthcare Mater 1: 729–735.
  • 118 Walmsley GG, McArdle A, Tevlin R, et al (2015). Nanotechnology in bone tissue engineering. Nanomedicine 11(5):12531263.
  • 119 Aston DE, Bow JR, Gangadean DN (2013). Mechanical properties of selected nanostructured materials and complex bio-nano, hybrid and hierarchical systems. Int Mater Rev 58(3): 167–202.
  • 120 Edmundson M, Thanh NT, Song B (2013). Nanoparticles based stem cell tracking in regenerative medicine. Theranostics 3(8): 573–582.
  • 121 Byambaa B, Annabi N, Yue K, et al (2017). Bioprinted osteogenic and vasculogenic patterns for engineering 3D bone tissue. Adv Healthc Mater 6(16): 1–15.
  • 122 Gladman AS, Matsumoto EA, Nuzzo RG, Mahadevan L, Lewis JA (2016). Biomimetic 4D printing. Nat Mater 15(4): 413–418.
  • 123 Tian L, Prabhakaran MP, Ramakrishna S (2015). Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules. Regen Biomater 2(1): 31–45.
  • 124 Masaeli E, Morshed M, Nasr-Esfahani MH, et al (2013). Fabrication, characterization and cellular compatibility of poly(hydroxy alkanoate) composite nanofibrous scaffolds for nerve tissue engineering. PLoS ONE 8(2): e57157.
  • 125 Reis LA, Chiu LL, Feric N, Fu L, Radisic M (2016). Biomaterials in myocardial tissue engineering. J Tissue Eng Regen Med 10(1): 11–28.
  • 126 Huyer LD, Montgomery M, Zhao Y, et al (2015). Biomaterial based cardiac tissue engineering and its applications. Biomed Mater 10(3): 034004.
  • 127 Chen FM, Liu X (2016). Advancing biomaterials of human origin for tissue engineering. Prog Polym Sci 53: 86–168.
  • 128 Nagueh SF, Shah G, Wu Y, et al (2004). Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation 110:155-162.
  • 129 Weis SM, Emery JL, Becker KD, McBride DJ, Omens JH, McCulloch AD (2000). Myocardial mechanics and collagen structure in the osteogenesis imperfecta murine (oim). Circ Res 87:663–669.
  • 130 Ott HC, Matthiesen TS, Goh SK, et al (2008). Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med 14:213–221.
  • 131 Sanchez PL, Fernandez-Santos ME, Costanza S, et al (2012). Characterization and biocompatibility of perfusiondecellularized human heart matrix: toward bioengineering perfusable human heart grafts. J Am Coll Cardiol 59:E857–E857.