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1. Alkaline activation of endogenous latent TGFβ1 by an injectable hydrogel directs cell homing for in situ complex tissue regeneration

Author

Wang, Sainan, Niu, Yuting, Jia, Peipei, Liao, Zheting, Guo, Weimin, Chaves, Rodrigo Cotrim, Tran-Ba, Khanh-Hoa, He, Ling, Bai, Hanying, Sia, Sam, Kaufman, Laura J, Wang, Xiaoyan, Zhou, Yongsheng, Dong, Yanmei, and Mao, Jeremy J

Subjects
Engineering, Biomedical Engineering, Bioengineering, Stem Cell Research, Dental/Oral and Craniofacial Disease, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Biotechnology, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Endogenous TGE beta 1, Injectable alkaline hydrogel, Cell homing, Pulp-dentin complex, In situ tissue regeneration, Endogenous TGFβ1, Medicinal and biomolecular chemistry, Biomedical engineering, Materials engineering
Abstract

Utilization of the body's regenerative potential for tissue repair is known as in situ tissue regeneration. However, the use of exogenous growth factors requires delicate control of the dose and delivery strategies and may be accompanied by safety, efficacy and cost concerns. In this study, we developed, for the first time, a biomaterial-based strategy to activate endogenous transforming growth factor beta 1 (TGFβ1) under alkaline conditions for effective in situ tissue regeneration. We demonstrated that alkaline-activated TGFβ1 from blood serum, bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable of increasing cell recruitment and early differentiation, implying its broad practicability. Furthermore, we engineered an injectable hydrogel (MS-Gel) consisting of gelatin microspheres for loading strong alkaline substances and a modified gelatin matrix for hydrogel click crosslinking. In vitro models showed that alkaline MS-Gel controllably and sustainably activated endogenous TGFβ1 from tooth dentin for robust bone marrow stem cell migration. More importantly, infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted significant pulp-dentin regeneration with neurovascular stroma and mineralized tissue by endogenous proliferative cells. Therefore, this work offers a new bench-to-beside translation strategy using biomaterial-activated endogenous biomolecules to achieve in situ tissue regeneration without the need for cell or protein delivery.

Published
2022

3. American Society for Bone and Mineral Research‐Orthopaedic Research Society Joint Task Force Report on Cell‐Based Therapies – Secondary Publication

Author

O'Keefe, Regis J, Tuan, Rocky S, Lane, Nancy E, Awad, Hani A, Barry, Frank, Bunnell, Bruce A, Colnot, Céline, Drake, Matthew T, Drissi, Hicham, Dyment, Nathaniel A, Fortier, Lisa A, Guldberg, Robert E, Kandel, Rita, Little, David G, Marshall, Mary F, Mao, Jeremy J, Nakamura, Norimasa, Proffen, Benedikt L, Rodeo, Scott A, Rosen, Vicki, Thomopoulos, Stavros, Schwarz, Edward M, and Serra, Rosa

Subjects
Engineering, Biomedical Engineering, Regenerative Medicine, Musculoskeletal, animal models, cell, tissue signaling, transcription factors, cells of bone, clinical trials, genetic research, cell/tissue signaling, Clinical Sciences, Human Movement and Sports Sciences, Orthopedics, Biomedical engineering, Sports science and exercise
Abstract

Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell-based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell-based therapies. The Task Force was charged with defining the state-of-the art in cell-based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell-based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:485-502, 2020.

Published
2020

4. American Society for Bone and Mineral Research‐Orthopaedic Research Society Joint Task Force Report on Cell‐Based Therapies

Author

O'Keefe, Regis J, Tuan, Rocky S, Lane, Nancy E, Awad, Hani A, Barry, Frank, Bunnell, Bruce A, Colnot, Céline, Drake, Matthew T, Drissi, Hicham, Dyment, Nathaniel A, Fortier, Lisa A, Guldberg, Robert E, Kandel, Rita, Little, David G, Marshall, Mary F, Mao, Jeremy J, Nakamura, Norimasa, Proffen, Benedikt L, Rodeo, Scott A, Rosen, Vicki, Thomopoulos, Stavros, Schwarz, Edward M, and Serra, Rosa

Subjects
Biomedical and Clinical Sciences, Regenerative Medicine, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Musculoskeletal, Advisory Committees, Bone and Bones, Humans, Minerals, Orthopedics, Societies, Medical, United States, ANIMAL MODELS, CELL, TISSUE SIGNALING, TRANSCRIPTION FACTORS, CELLS OF BONE, CLINICAL TRIALS, GENETIC RESEARCH, CELL/TISSUE SIGNALING, CELL/TISSUE SIGNALING, TRANSCRIPTION FACTORS, Biological Sciences, Engineering, Medical and Health Sciences, Anatomy & Morphology, Biological sciences, Biomedical and clinical sciences
Abstract

Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell-based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell-based therapies. The Task Force was charged with defining the state-of-the art in cell-based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell-based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2019 American Society for Bone and Mineral Research.

Published
2020

9. List of contributors

Author

Abe, Masashi, primary, Ahlstrom, Jon D., additional, Albon, Julie, additional, Allickson, Julie, additional, Almeida-Porada, Graça, additional, Altschuler, Richard A., additional, Anderson, Daniel G., additional, Annabi, Nasim, additional, Arcidiacono, Judith, additional, Ashammakhi, Nureddin, additional, Atala, Anthony, additional, Athanasiou, Kyriacos A., additional, Awad, Hani A., additional, Badylak, Stephen F, additional, Balachander, Gowri, additional, Balkan, Wayne, additional, Bara, Jennifer J., additional, Barry, Michael P., additional, Baskaran, Harihara, additional, Bedell, Matthew L., additional, Belcher, Donald Andrew, additional, Berry, David B., additional, Bhat, Hina, additional, Bhat, Zuhaib F., additional, Bhatia, Sangeeta N., additional, Blackburn, Catherine Clare, additional, Blocki, Anna, additional, Blum, Kevin M., additional, Bochenek, Matthew A., additional, Bonassar, Lawrence J., additional, Bonventre, Joseph V., additional, Borrelli, Mimi R., additional, Bowles, Robby D., additional, Bradshaw, Amy D., additional, Bratt-Leal, Andres M., additional, Breuer, Christopher K., additional, Brewster, Luke, additional, Brey, Eric M., additional, Briquez, Priscilla S., additional, Buckwalter, J.A., additional, Burg, Karen J.L., additional, Burg, Timothy C., additional, Byambaa, Batzaya, additional, Chandra, Prafulla K., additional, Chen, Amanda X., additional, Chen, Fa-Ming, additional, Chen, Shaochen, additional, Chesterman, Julian, additional, Chhabra, Arnav, additional, Chong, Seow Khoon, additional, Clark, Richard A.F., additional, Cleary, Muriel A., additional, Coleman, M., additional, Cotsarelis, George, additional, Crystal, Ronald G., additional, Dagnelie, Gislin, additional, Darabi, Mohammad Ali, additional, Davidson, Jeffrey M., additional, Davidson, Joseph, additional, De Coppi, Paolo, additional, Delcassian, Derfogail, additional, de Vos, Paul, additional, Dominijanni, Anthony, additional, Donahue, Ryan, additional, Drain, Allison P., additional, Duvall, Craig L., additional, Dziki, Jenna L., additional, Elgalad, Abdelmotagaly, additional, Eng, George, additional, Falanga, Vincent, additional, Farhang, Niloofar, additional, Ferreira, Lino, additional, Fink, Donald W., additional, Fleming, Heather E., additional, Fong, Peter, additional, Frey, Mark R., additional, Gay, Denise, additional, Gerecht, Sharon, additional, Gersbach, Charles A., additional, Gibbs, D.M.R., additional, Gidwani, Simran, additional, González Morales, Shaimar R., additional, Goyal, Ritu, additional, Grant, Maria B., additional, Gray, Andrea, additional, Greisler, Howard P., additional, Grikscheit, Tracy C., additional, Grosh, Karl, additional, Guilak, Farshid, additional, Guo, Jason L., additional, Han, Yingli, additional, Hare, Joshua M., additional, Hassanbhai, Ammar Mansoor, additional, Hatzistergos, Konstantinos, additional, Hay, David C., additional, He, Xiao-Tao, additional, Henderson, Timothy, additional, Hickerson, Darren, additional, Hickerson, Darren H.M., additional, Hmadcha, Abdelkrim, additional, Hochman-Mendez, Camila, additional, Huang, Chao, additional, Hubbell, Jeffrey A., additional, Huelsmann, Joern, additional, Huh, Jun Tae, additional, Hunsberger, Joshua G., additional, Iannucci, Leanne E., additional, Inoue, Haruhisa, additional, Jackson, John, additional, Jiang, Yangzi, additional, Kalinichenko, Vladimir V., additional, Kanczler, J.M., additional, Karp, Jeffrey M., additional, Kasper, F. Kurtis, additional, Khademhosseini, Ali, additional, Kim, Ji Hyun, additional, Kimbrel, Erin A., additional, Klimanskaya, Irina, additional, Kohn, Joachim, additional, Kumar, Sunil, additional, Kyriakides, Themis R., additional, Lake, Spencer P., additional, Lam, Johnny, additional, Langer, Robert, additional, Lanza, Robert, additional, Leach, Timothy S., additional, Lee, Benjamin W., additional, Lee, Iris, additional, Lee, Sang Jin, additional, Li, David, additional, Li, Linheng, additional, Liu, Qian, additional, Ljubimov, Alexander V., additional, Lo, Chi, additional, Longaker, Michael T., additional, López-Beas, Javier, additional, Loring, Jeanne F., additional, Luo, Ying, additional, MacArthur, Ben D., additional, Madigan, Nicolas N., additional, Madry, Henning, additional, Magalhaes, Renata S., additional, Manley, Nancy Ruth, additional, Mansbridge, Jonathan, additional, Mao, Jeremy J., additional, Marshall, K.M., additional, Martin, J.A., additional, Martins-Green, M., additional, Maselli, Kathryn M., additional, Maxfield, Mark W., additional, McCracken, Kyle W., additional, Melville, James, additional, Mikos, Antonios G., additional, Millán, José del R., additional, Mirotsou, Maria, additional, Montoro, Daniel T., additional, Murphy, Matthew P., additional, Murphy, Sean V., additional, Musillo, Michael, additional, Muthukumaran, Padmalosini, additional, Navara, Adam M., additional, Nelson, Christopher E., additional, Niklason, Laura E., additional, Nowell, Craig Scott, additional, O’Keefe, Regis J., additional, O’Neill, Kathy E., additional, Oreffo, Richard O.C., additional, Ortiz, Ophir, additional, Palmer, Andre Francis, additional, Perdikis, Serafeim, additional, Petreaca, M., additional, Plikus, Maksim V., additional, Porada, Christopher D., additional, Post, Mark, additional, Prokop, Aleš, additional, Puri, Raj K., additional, Qian, Pengxu, additional, Radisic, Milica, additional, Raredon, Micha Sam Brickman, additional, Richie, Ellen Rothman, additional, Rouse, Paul, additional, Sadri-Ardekani, Hooman, additional, Saltzman, W. Mark, additional, Sampaio, Luiz C., additional, Schlieve, Christopher R., additional, Sha, Su-Hua, additional, Sharpe, Paul T., additional, Shastri, V. Prasad, additional, Shi, Yanhong, additional, Shupe, Thomas, additional, Sirabella, Dario, additional, Skardal, Aleksander, additional, Slack, J.M.W., additional, Sloan, Stephen R., additional, Soker, Shay, additional, Soria, Bernat, additional, Soria-Juan, Bárbara, additional, Stockdale, Frank E., additional, Stover, Josh, additional, Stransky, Thomas, additional, Stronks, H. Christiaan, additional, Stumpf, Patrick S., additional, Sung, Kyung Eun, additional, Swarr, Daniel, additional, Szkolnicka, Dagmara, additional, Takahashi, Jun, additional, Tang, D.K.O., additional, Tang, Winson, additional, Taylor, Doris A., additional, Teng, Yao, additional, Teoh, Swee Hin, additional, Smith, Anthony J., additional, Treffeisen, Elsa, additional, Tuan, Rocky S., additional, Vacanti, Joseph P., additional, van der Weele, Cor, additional, Vincent, Matthew, additional, Vunjak-Novakovic, Gordana, additional, Wahlberg, Lars U., additional, Wan, Derrick C., additional, Wang, Anne, additional, Wang, Dan, additional, Wang, Qiwei, additional, Wang, Yanling, additional, Wang, Yu-li, additional, Wang, Zhanwen, additional, Weaver, Valerie M., additional, Wells, J.A., additional, Welter, Jean F., additional, Wen, Feng, additional, Weston, Jake, additional, Whitsett, Jeffrey A., additional, Williams, James K., additional, Windebank, Anthony J., additional, Wong, Mark Eu-Kien, additional, Worgall, Stefan, additional, Wu, Iwen, additional, Wu, Rui-Xin, additional, Xie, Virginia Y., additional, Xing, Malcolm, additional, Yamada, Kenneth M., additional, Yamanaka, Shinya, additional, Yoo, James J., additional, Young, Simon, additional, Yu, Claire, additional, Yu, Hanry, additional, Yuan, Yifan, additional, Zacharias, William, additional, Zakko, Jason, additional, Zhang, Ai, additional, Zhang, Yuanyuan, additional, Zhang, Zheng, additional, Zhao, Chunfeng, additional, Zhao, Yimu, additional, and Zoloth, Laurie, additional

Published
2020
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10. 3D-Printed Artificial Meniscus

Author

Nakagawa, Yusuke, Fortier, Lisa A., Mao, Jeremy J., Sekiya, Ichiro, Rodeo, Scott A., Gobbi, Alberto, editor, Espregueira-Mendes, João, editor, Lane, John G., editor, and Karahan, Mustafa, editor

Published
2017
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13. Alkaline activation of endogenous latent TGFβ1 by an injectable hydrogel directs cell homing for in situ complex tissue regeneration

Author

Wang, Sainan, primary, Niu, Yuting, additional, Jia, Peipei, additional, Liao, Zheting, additional, Guo, Weimin, additional, Chaves, Rodrigo Cotrim, additional, Tran-Ba, Khanh-Hoa, additional, He, Ling, additional, Bai, Hanying, additional, Sia, Sam, additional, Kaufman, Laura J., additional, Wang, Xiaoyan, additional, Zhou, Yongsheng, additional, Dong, Yanmei, additional, and Mao, Jeremy J., additional

Published
2022
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26. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine

Author

Bianco, Paolo, Cao, Xu, Frenette, Paul S., Mao, Jeremy J., Robey, Pamela G., Simmons, Paul J., and Wang, Cun-Yu

Subjects
Stem cells -- Health aspects -- Properties, Stem cell research -- Evaluation, Biological sciences, Health
Abstract

Mesenchymal stem cells (MSCs) are the focus of intensive efforts worldwide directed not only at elucidating their nature and unique properties but also developing cell-based therapies for a diverse range of diseases. More than three decades have passed since the original formulation of the concept, revolutionary at the time, that multiple connective tissues could emanate from a common progenitor or stem cell retained in the postnatal bone marrow. Despite the many important advances made since that time, substantial ambiguities still plague the field regarding the nature, identity, function, mode of isolation and experimental handling of MSCs. These uncertainties have a major impact on their envisioned therapeutic use., Narrowing the focus on the stem cell Unbeknown to most readers of the copious literature dealing with both fundamental and clinical aspects of MSC biology, the current, widespread general concept [...]

Published
2013
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27. List of Contributors

Author

Bowles, Robby D., primary, (Tony) Smith, Anthony J., additional, Ahlstrom, Jon D., additional, Albon, Julie, additional, Alexander, Peter G., additional, Altschuler, Richard A., additional, Alvarez, Pedro, additional, Amendola, A., additional, Anatol, Rachael, additional, Annabi, Nasim, additional, Anversa, Piero, additional, Arcidiacono, Judith, additional, Atala, Anthony, additional, Athanasiou, Kyriacos A., additional, Auger, François A., additional, Auguste, Debra T., additional, Awad, Hani A., additional, Badylak, Stephen F., additional, Bailey, Alexander M., additional, Barry, Michael P., additional, Becker, Daniel, additional, Belegu, Visar, additional, Bernhard, Jonathan, additional, Bertram, Timothy, additional, Besnard, Valérie, additional, Bhat, Z.F., additional, Bhat, Hina, additional, Bhatia, Sangeeta N., additional, Bhumiratana, Sarindr, additional, Bianco, Paolo, additional, Blackburn, Catherine Clare, additional, Bollenbach, Thomas, additional, Bonassar, Lawrence A., additional, Boulton, Mike, additional, Bradshaw, Amy D., additional, Breuer, Christopher K., additional, Brewster, Luke, additional, Brey, Eric M., additional, Brittan, Mairi, additional, Brown, Bryan N., additional, Brown, T., additional, Buckwalter, J.A., additional, Buffington, Deborah, additional, Burg, Karen J.L., additional, Burg, Timothy C., additional, Chabaud, Stéphane, additional, Swi Chang, Thomas Ming, additional, Chang, Yunchao, additional, Chapman, Robert G., additional, Chen, Fa-Ming, additional, Chen, Una, additional, Cimetta, Elisa, additional, Clark, Richard A.F., additional, Clark, Karen L., additional, Cleary, Muriel A., additional, Cloutier, Réjean, additional, Colton, Clark K., additional, Cotsarelis, George, additional, Crystal, Ronald G., additional, Dagnelie, Gislin, additional, da Silva Ferreira, Lino, additional, Davidson, Jeffrey M., additional, Deuel, Thomas F., additional, Direkze, Natalie, additional, Dressler, Gregory R., additional, Durfor, Charles N., additional, Duvall, Craig L., additional, Eng, George, additional, Engelmayr, George, additional, Eschenhagen, Thomas, additional, Eu-Kien Wong, Mark, additional, Falanga, Vincent, additional, Faria, Katie, additional, Faustman, Denise L., additional, Fauza, Dario O., additional, Feng, Qiang, additional, Ferreira, Lino, additional, Fink, Donald W., additional, Fissell, William, additional, Freed, Lisa E., additional, Furth, Mark E., additional, Gay, Denise, additional, Gerecht-Nir, Sharon, additional, Germain, Lucie, additional, Gersbach, Charles A., additional, Goulet, Francine, additional, Goyal, Ritu, additional, Grant, Maria B., additional, Greisler, Howard P., additional, Guilak, Farshid, additional, Harley, Brendan A.C., additional, Hart, David A., additional, Hmadcha, Abdelkrim, additional, Hodges, Steve J., additional, Hofer, Heidi R., additional, Hollinger, Jeffrey O., additional, Holobaugh, Patricia, additional, Hubbell, Jeffrey A., additional, Humes, H. David, additional, Ingber, Donald E., additional, Inskeep, Beau, additional, Jiang, Xingyu, additional, Kajstura, Jan, additional, Kane, Ravi S., additional, Karp, Jeffrey M., additional, Kasper, F. Kurtis, additional, Khademhosseini, Ali, additional, Kili, Sven, additional, Kimbrel, Erin A., additional, Klimanskaya, Irina, additional, Kohn, Joachim, additional, Kunisaki, Shaun M., additional, Kyriakides, Themis R., additional, Lagasse, Eric, additional, Lamontagne, Jean, additional, Langer, Robert, additional, Lanza, Robert, additional, Lecht, Shimon, additional, Lee, Benjamin W., additional, Lee, Chang H., additional, Lee, Mark H., additional, Lelkes, Peter I., additional, Leri, Annarosa, additional, Levine, David W., additional, Li, Feng, additional, Longaker, Michael T., additional, López, Javier, additional, Lu, Shi-Jiang, additional, Luo, Ying, additional, MacArthur, Ben D., additional, Manley, Nancy Ruth, additional, Manohar, Rohan, additional, Mansbridge, Jonathan, additional, Mantalaris, Athanasios, additional, Mao, Jeremy J., additional, Marsh, J.L., additional, Martin, David C., additional, Martin, J.A., additional, Martins-Green, M., additional, Masuda, Koichi, additional, Maxfield, Mark W., additional, McCabe, Kathryn L., additional, McDonald, John W., additional, McFarland, Richard, additional, Mikos, Antonios G., additional, Millán, José del R., additional, Miller, Josef M., additional, Mills, Shari, additional, Moffat, Kristen L., additional, Mondrinos, Mark J., additional, Montoro, Daniel T., additional, Moore, Malcolm A.S., additional, Neal, Rebekah A., additional, Nerem, Robert M., additional, Ng, Shengyong, additional, Nowell, Craig Scott, additional, Obokata, Haruko, additional, Olsen, Bjorn Reino, additional, Oreffo, Richard O.C., additional, O’Keefe, Regis J., additional, O’Neill, Kathy, additional, Ortiz, Ophir, additional, Pan, Carolyn K., additional, Pathak, Vikas, additional, Petreaca, M., additional, Pezzolla, Daniela, additional, Plikus, Maksim V., additional, Polak, Julia M., additional, Post, Mark, additional, Preston, Sean, additional, Prokop, Aleš, additional, Radisic, Milica, additional, Ranghini, Egon, additional, Raphael, Yehoash, additional, Reddi, A.H., additional, Reichenspurner, Herrmann, additional, Richie, Ellen, additional, Robey, Pamela Gehron, additional, Robinson, Becky, additional, Rojas, Anabel, additional, Roy, Shuvo, additional, Russell, Alan J., additional, Saigal, Rajiv, additional, Saltzman, W. Mark, additional, Samadikuchaksaraei, Ali, additional, Sambanis, Athanassios, additional, Schacht, Jochen, additional, Schutte, Stacey C., additional, Schutte, Lyndsey, additional, Schwartz, Steven D., additional, Schwartz, Robert E., additional, Setton, Lori A., additional, Sha, Su-Hua, additional, Shan, Jing, additional, Sharpe, Paul T., additional, Shi, Songtao, additional, Shrivats, Arun R., additional, Simon, Franck, additional, Sirabella, Dario, additional, Slack, J.M.W., additional, Soria, Bernat, additional, Spicer, Patrick, additional, Stevens, Kelly R., additional, Stockdale, Frank E., additional, Christiaan Stronks, H., additional, Studer, Lorenz, additional, Takayama, Shuichi, additional, Thomson, James A., additional, Trachtenberg, Jordan E., additional, Treffeisen, Elsa, additional, Tuan, Rocky S., additional, Vacanti, Charles A., additional, Vacanti, Joseph P., additional, van der Weele, Cor, additional, Vincent, Matthew, additional, Vunjak-Novakovic, Gordana, additional, Wahlberg, Lars U., additional, Wan, Derrick C., additional, Wang, Anne, additional, Westover, Angela J., additional, Whitesides, George M., additional, Whitsett, Jeffrey A., additional, Winitsky, Steve, additional, Witten, Celia, additional, Worgall, Stefan, additional, Wright, Nicholas A., additional, Yannas, Ioannis V., additional, Young, Simon, additional, Yu, Junying, additional, Zhang, Zheng, additional, Zheng, Wenfu, additional, Zimmermann, Wolfram Hubertus, additional, and Zoloth, Laurie, additional

Published
2014
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32. CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model

Author

Lee, Chang H., Shah, Bhranti, Moioli, Eduardo K., and Mao, Jeremy J.

Subjects
Healing -- Research, Stem cells -- Properties, Fibroblasts -- Properties, Cell differentiation -- Research, Growth factors -- Properties, Health care industry
Abstract

Fibroblasts are ubiquitous cells that demonstrate remarkable diversity. However, their origin and pathways of differentiation remain poorly defined. Here, we show that connective tissue growth factor (CTGF; also known as CCN2) is sufficient to induce human bone marrow mesenchymal stem/stromal cells (MSCs) to differentiate into fibroblasts. CTGF-stimulated MSCs lost their surface mesenchymal epitopes, expressed broad fibroblastic hallmarks, and increasingly synthesized collagen type I and tenacin-C. After fibroblastic commitment, the ability of MSCs to differentiate into nonfibroblastic lineages--including osteoblasts, chondrocytes, and adipocytes--was diminished. To address inherent heterogeneity in MSC culture, we established 18 single MSC-derived clones by limiting dilution. CTGF-treated MSCs were α-[SMA.sup.-], differentiating into α-[SMA.sup.+] myofibroblasts only when stimulated subsequently with TGF-β1, suggestive of stepwise processes of fibroblast commitment, fibrogenesis, and pathological fibrosis. In rats, in vivo microencapsulated delivery of CTGF prompted postnatal connective tissue to undergo fibrogenesis rather than ectopic mineralization. The knowledge that fibroblasts have a mesenchymal origin may enrich our understanding of organ fibrosis, cancer stroma, ectopic mineralization, scarring, and regeneration., Introduction Fibroblasts are ubiquitous cells that constitute the stroma of virtually all tissues. The conventional view of fibroblasts as no more than collagen-producing cells is being challenged by their interactions [...]

Published
2010
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48. Contributor contact details

Author

Ferri, Joël, primary, Hunziker, Ernst B., additional, Meyer, Ulrich, additional, Wiesmann, Hans Peter, additional, Neunzehn, Jörg, additional, Joos, Ulrich, additional, Stoelinga, Paul J.W., additional, Cawood, John I., additional, Tulasne, J.F., additional, Acero, Julio, additional, Goga, Dominique, additional, Sury, Florent, additional, Tayeb, Talel, additional, Ferri, Joël, additional, Lauwers, Ludovic, additional, Iizuka, Tateyuki, additional, Takahashi, Tetsu, additional, Yamauchi, Kensuke, additional, Elia, P., additional, Dubois, H., additional, Ferri, J., additional, Wojcik, Thomas, additional, Raoul, Gwenael, additional, Desmet, B., additional, Breton, P., additional, Seigneuric, J-B., additional, Vazquez, M-P., additional, Froget, Nicolas, additional, Pierrefeu, Antoine, additional, Koppe, Matthieu, additional, Breton, Pierre, additional, Leconte, M., additional, Wojcik, T., additional, Mongeot, M., additional, Neiva, Rodrigo, additional, Giannobile, William V., additional, Hunziker, E.B., additional, Simon, Stéphane, additional, Cooper, Paul, additional, Isaac, Julianne, additional, Berdal, Ariane, additional, and Mao, Jeremy J., additional

Published
2011
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