Osteogenic commitment of human induced pluripotent stem cell-derived mesenchymal progenitor-like cells on biomimetic scaffolds

Eun-Seo Lee; Jungha Park; Jane Wang; Hwajin Lee; Nathaniel S. Hwang

Journal of Industrial and Engineering Chemistry, Vol.37, 147-155, May, 2016

DOI10.1016/j.jiec.2016.03.017 Export Citation

Osteogenic commitment of human induced pluripotent stem cell-derived mesenchymal progenitor-like cells on biomimetic scaffolds

Eun-Seo Lee, Jungha Park, Jane Wang¹, Hwajin Lee^{2, †}, and Nathaniel S. Hwang^†

School of Chemical and Engineering, Institute of Chemical Processes, N-Bio Institute, Seoul National University, Seoul, South Korea
¹Department of Chemical Engineering, National Tsing Hua University, Taiwan
²Cellular and Molecular Medicine Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD, USA

E-mail:,

In this study, mesenchymal progenitor-like cells (MPLCs) were derived from human induced pluripotent stem cells (hiPSCs) by retinoic acid (RA) treatment. In particular, RA induced hiPSC-derived MPLCs were able to efficiently committed into osteogenic lineage cells. In addition, hiPSC-MPLCs were seeded onto three-dimensional biomimetic scaffolds composed of hydroxyapatite and poly(L-lactic acid)/poly(lactic-co-glycolide) for assessing osteoinductivity, and enhanced osteogenic activities were perceived in RA-treated cells in vitro and in vivo. In conclusion, addition of RA increased the osteogenic commitment potential of hiPSCs-MPLCs and further applications with biomimetic composite scaffolds showed a promising combination for bone tissue engineering applications.

Keywords:Bone tissue engineering;Hydroxyapatite;Retinoic acid;Human induced pluripotent stem cells;Mesenchymal progenitor-like cells

[References]

Damien CJ, Parsons JR, J. Appl. Biomater., 2, 187 (1991)
Rose FRAJ, Oreffo ROC, Biochem. Biophys. Res. Commun., 292(1), 1 (2002)
Tiedeman JJ, Garvin KL, Kile TA, Connolly JF, Orthopedics, 18, 1153 (1995)
Katti KS, Colloids Surf. B: Biointerfaces, 39, 133 (2004)
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM, Nature, 418, 41 (2002)
Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH, Blood, 103, 1669 (2004)
Gimble J, Guilak F, Cytotherapy, 5, 362 (2003)
Tuan RS, Boland G, Tuli R, Arthr. Res. Ther., 5, 32 (2003)
Payne KA, Didiano DM, Chu CR, Osteoarthr. Cartil./OARS Osteoarthr. Res. Soc., 18, 705 (2010)
Stenderup K, Justesen J, Clausen C, Kassem M, Bone, 33, 919 (2003)
Hwang NS, Varghese S, Lee HJ, Zhang Z, Ye Z, Bae J, Cheng L, Elisseeff J, Proc. Natl. Acad. Sci. U.S.A., 105, 20641 (2008)
Barberi T, Willis LM, Socci ND, Studer L, PLoS Med., 2, e161 (2005)
Jung Y, Bauer G, Nolta JA, Stem Cells, 30, 42 (2012)
Dang SM, Kyba M, Perlingeiro R, Daley GQ, Zandstra PW, Biotechnol. Bioeng., 78(4), 442 (2002)
Brown SE, Tong W, Krebsbach PH, Cells Tissues Organs, 189, 256 (2009)
Takashima Y, Era T, Nakao K, Kondo S, Kasuga M, Smith AG, Nishikawa S, Cell, 129, 1377 (2007)
Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM, Nature, 345, 224 (1990)
Napoli JL, Clin. Immunol. Immunopathol., 80, S52 (1996)
Bain G, Kitchens D, Yao M, Huettner JE, Gottlieb DI, Dev. Biol., 168, 342 (1995)
Groeneveld EH, van den Bergh JP, Holzmann P, ten Bruggenkate CM, Tuinzing DB, Burger EH, J. Biomed. Mater. Res., 48, 393 (1999)
Hutmacher DW, Schantz JT, Lam CX, Tan KC, Lim TC, J. Tissue Eng. Regen. Med., 1, 245 (2007)
Hutmacher DW, Biomaterials, 21, 2529 (2000)
LeGeros RZ, Clin. Mater., 14, 65 (1993)
Kim HW, Lee HH, Knowles JC, J. Biomed. Mater. Res. Part A, 79, 643 (2006)
Shikinami Y, Okuno M, Biomaterials, 20, 859 (1999)
Petricca SE, Marra KG, Kumta PN, Acta Biomater., 2, 277 (2006)
Pankratz MT, Li XJ, Lavaute TM, Lyons EA, Chen X, Zhang SC, Stem Cells, 25, 1511 (2007)
Takahashi K, Yamanaka S, Cell, 126, 663 (2006)
Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA, Cell Stem Cell, 12, 252 (2013)
Darabi R, Arpke RW, Irion S, Dimos JT, Grskovic M, Kyba M, Perlingeiro RC, Cell Stem Cell, 10, 610 (2012)
Zhang X, Hirai M, Cantero S, Ciubotariu R, Dobrila L, Hirsh A, Igura K, Satoh H, Yokomi I, Nishimura T, Yamaguchi S, Yoshimura K, Rubinstein P, Takahashi TA, J. Cell. Biochem., 112, 1206 (2011)
Dominici M, Blanc KL, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E, Cytotherapy, 8, 315 (2006)
Kuboki Y, Takita H, Kobayashi D, Tsuruga E, Inoue M, Murata M, Nagai N, Dohi Y, Ohgushi H, J. Biomed. Mater. Res., 39, 190 (1998)
Mikos AG, Thorsen AJ, Czerwonka LA, Bao Y, Langer R, Winslow DN, Vacanti JP, Polymer, 35(5), 1068 (1994)
Komori T, Adv. Exp. Med. Biol., 658, 43 (2010)
Im JY, Min WK, You C, Kim HO, Jin HK, Bae JS, Lab. Anim. Res., 29, 196 (2013)

[1] Damien CJ, Parsons JR, J. Appl. Biomater., 2, 187 (1991)

[2] Rose FRAJ, Oreffo ROC, Biochem. Biophys. Res. Commun., 292(1), 1 (2002)

[3] Tiedeman JJ, Garvin KL, Kile TA, Connolly JF, Orthopedics, 18, 1153 (1995)

[4] Katti KS, Colloids Surf. B: Biointerfaces, 39, 133 (2004)

[5] Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM, Nature, 418, 41 (2002)

[6] Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH, Blood, 103, 1669 (2004)

[7] Gimble J, Guilak F, Cytotherapy, 5, 362 (2003)

[8] Tuan RS, Boland G, Tuli R, Arthr. Res. Ther., 5, 32 (2003)

[9] Payne KA, Didiano DM, Chu CR, Osteoarthr. Cartil./OARS Osteoarthr. Res. Soc., 18, 705 (2010)

[10] Stenderup K, Justesen J, Clausen C, Kassem M, Bone, 33, 919 (2003)

[11] Hwang NS, Varghese S, Lee HJ, Zhang Z, Ye Z, Bae J, Cheng L, Elisseeff J, Proc. Natl. Acad. Sci. U.S.A., 105, 20641 (2008)

[12] Barberi T, Willis LM, Socci ND, Studer L, PLoS Med., 2, e161 (2005)

[13] Jung Y, Bauer G, Nolta JA, Stem Cells, 30, 42 (2012)

[14] Dang SM, Kyba M, Perlingeiro R, Daley GQ, Zandstra PW, Biotechnol. Bioeng., 78(4), 442 (2002)

[15] Brown SE, Tong W, Krebsbach PH, Cells Tissues Organs, 189, 256 (2009)

[16] Takashima Y, Era T, Nakao K, Kondo S, Kasuga M, Smith AG, Nishikawa S, Cell, 129, 1377 (2007)

[17] Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM, Nature, 345, 224 (1990)

[18] Napoli JL, Clin. Immunol. Immunopathol., 80, S52 (1996)

[19] Bain G, Kitchens D, Yao M, Huettner JE, Gottlieb DI, Dev. Biol., 168, 342 (1995)

[20] Groeneveld EH, van den Bergh JP, Holzmann P, ten Bruggenkate CM, Tuinzing DB, Burger EH, J. Biomed. Mater. Res., 48, 393 (1999)

[21] Hutmacher DW, Schantz JT, Lam CX, Tan KC, Lim TC, J. Tissue Eng. Regen. Med., 1, 245 (2007)

[22] Hutmacher DW, Biomaterials, 21, 2529 (2000)

[23] LeGeros RZ, Clin. Mater., 14, 65 (1993)

[24] Kim HW, Lee HH, Knowles JC, J. Biomed. Mater. Res. Part A, 79, 643 (2006)

[25] Shikinami Y, Okuno M, Biomaterials, 20, 859 (1999)

[26] Petricca SE, Marra KG, Kumta PN, Acta Biomater., 2, 277 (2006)

[27] Pankratz MT, Li XJ, Lavaute TM, Lyons EA, Chen X, Zhang SC, Stem Cells, 25, 1511 (2007)

[28] Takahashi K, Yamanaka S, Cell, 126, 663 (2006)

[29] Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA, Cell Stem Cell, 12, 252 (2013)

[30] Darabi R, Arpke RW, Irion S, Dimos JT, Grskovic M, Kyba M, Perlingeiro RC, Cell Stem Cell, 10, 610 (2012)

[31] Zhang X, Hirai M, Cantero S, Ciubotariu R, Dobrila L, Hirsh A, Igura K, Satoh H, Yokomi I, Nishimura T, Yamaguchi S, Yoshimura K, Rubinstein P, Takahashi TA, J. Cell. Biochem., 112, 1206 (2011)

[32] Dominici M, Blanc KL, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E, Cytotherapy, 8, 315 (2006)

[33] Kuboki Y, Takita H, Kobayashi D, Tsuruga E, Inoue M, Murata M, Nagai N, Dohi Y, Ohgushi H, J. Biomed. Mater. Res., 39, 190 (1998)

[34] Mikos AG, Thorsen AJ, Czerwonka LA, Bao Y, Langer R, Winslow DN, Vacanti JP, Polymer, 35(5), 1068 (1994)

[35] Komori T, Adv. Exp. Med. Biol., 658, 43 (2010)

[36] Im JY, Min WK, You C, Kim HO, Jin HK, Bae JS, Lab. Anim. Res., 29, 196 (2013)