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4. A fully defined matrix to support a pluripotent stem cell derived multi-cell-liver steatohepatitis and fibrosis model

Author

Kumar, Manoj, Toprakhisar, Burak, Van Haele, Matthias, Antoranz, Asier, Boon, Ruben, Chesnais, Francois, De Smedt, Jonathan, Tricot, Tine, Idoype, Teresa Izuel, Canella, Marco, Tilliole, Pierre, De Boeck, Jolan, Bajaj, Manmohan, Ranga, Adrian, Bosisio, Francesca Maria, Roskams, Tania, van Grunsven, Leo A., and Verfaillie, Catherine M.

Published
2021
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5. Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling.

Author

Chui, Jonathan Sai‐Hong, Izuel‐Idoype, Teresa, Qualizza, Alessandra, de Almeida, Rita Pires, Piessens, Lindsey, van der Veer, Bernard K., Vanmarcke, Gert, Malesa, Aneta, Athanasouli, Paraskevi, Boon, Ruben, Vriens, Joris, van Grunsven, Leo, Koh, Kian Peng, Verfaillie, Catherine M., and Lluis, Frederic

Subjects
HUMAN cell cycle, WNT signal transduction, CELL differentiation, CELL cycle, PLURIPOTENT stem cells, GROWTH
Abstract

Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to differentiate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces a protective p53‐independent quiescent state in immature hepatoma cells and in pluripotent stem cell‐derived models of human hepatocytes and endothelial cells. Prolonged culture in hyperosmolar conditions stimulates changes in gene expression promoting functional cell maturation. Interestingly, hyperosmolar conditions do not only trigger growth arrest and cellular maturation but are also necessary to maintain this maturated state, as switching back to plasma osmolarity reverses the changes in expression of maturation and proliferative markers. Transcriptome analysis revealed sequential stages of osmolarity‐regulated growth arrest followed by cell maturation, mediated by activation of NF‐κВ, and repression of WNT signaling, respectively. This study reveals that a modulated increase in osmolarity serves as a biochemical signal to promote long‐term growth arrest and cellular maturation into different lineages, providing a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines

Author

Boon, Ruben, Kumar, Manoj, Tricot, Tine, Elia, Ilaria, Ordovas, Laura, Jacobs, Frank, One, Jennifer, De Smedt, Jonathan, Eelen, Guy, Bird, Matthew, Roelandt, Philip, Doglioni, Ginevra, Vriens, Kim, Rossi, Matteo, Vazquez, Marta Aguirre, Vanwelden, Thomas, Chesnais, François, El Taghdouini, Adil, Najimi, Mustapha, Sokal, Etienne, Cassiman, David, Snoeys, Jan, Monshouwer, Mario, Hu, Wei-Shou, Lange, Christian, Carmeliet, Peter, Fendt, Sarah-Maria, and Verfaillie, Catherine M.

Published
2020
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14. Dystrophin deficiency leads to dysfunctional glutamate clearance in iPSC derived astrocytes

Author

Patel, Abdulsamie M., Wierda, Keimpe, Thorrez, Lieven, van Putten, Maaike, De Smedt, Jonathan, Ribeiro, Luis, Tricot, Tine, Gajjar, Madhavsai, Duelen, Robin, Van Damme, Philip, De Waele, Liesbeth, Goemans, Nathalie, Tanganyika-de Winter, Christa, Costamagna, Domiziana, Aartsma-Rus, Annemieke, van Duyvenvoorde, Hermine, Sampaolesi, Maurilio, Buyse, Gunnar M., and Verfaillie, Catherine M.

Published
2019
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19. Mesodermal iPSC-derived progenitor cells functionally regenerate cardiac and skeletal muscle

Author

Quattrocelli, Mattia, Swinnen, Melissa, Giacomazzi, Giorgia, Camps, Jordi, Barthelemy, Ines, Ceccarelli, Gabriele, Caluwe, Ellen, Grosemans, Hanne, Thorrez, Lieven, Pelizzo, Gloria, Muijtjens, Manja, Verfaillie, Catherine M., Blot, Stephane, Janssens, Stefan, and Sampaolesi, Maurilio

Subjects
Medical research, Medicine, Experimental, Muscles -- Regeneration, Stem cells -- Health aspects, Cell differentiation -- Health aspects, Health care industry
Abstract

Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles., Introduction Induced pluripotent stem cells (iPSCs) represent a promising contribution to regenerative medicine (1). Despite the regulatory hurdles and safety issues involved, reprogramming patients' cells into iPSCs for autologous cell [...]

Published
2015
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28. Fetal hematopoietic stem cell homing is controlled by VEGF regulating the integrity and oxidative status of the stromal-vascular bone marrow niches

Author

Mesnieres, Marion, primary, Böhm, Anna-Marei, additional, Peredo, Nicolas, additional, Trompet, Dana, additional, Valle-Tenney, Roger, additional, Bajaj, Manmohan, additional, Corthout, Nikky, additional, Nefyodova, Elena, additional, Cardoen, Ruben, additional, Baatsen, Pieter, additional, Munck, Sebastian, additional, Nagy, Andras, additional, Haigh, Jody J., additional, Khurana, Satish, additional, Verfaillie, Catherine M., additional, and Maes, Christa, additional

Published
2021
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34. Multipotent adult progenitor cells sustain function of ischemic limbs in mice

Author

Aranguren, Xabier L., McCue, Jonathan D., Hendrickx, Benoit, Zhu, Xiao-Hong, Du, Fei, Chen, Eleanor, Pelacho, Beatriz, Penuelas, Ivan, Abizanda, Gloria, Uriz, Maialen, Frommer, Sarah A., Ross, Jeffrey J., Schroeder, Betsy A., Seaborn, Meredith S., Adney, Joshua R., Hagenbrock, Julianna, Harris, Nathan H., Zhang, Yi, Zhang, Xiaoliang, Nelson-Holte, Molly H., Jiang, Yuehua, Billiau, An D., Chen, Wei, Prosper, Felipe, Verfaillie, Catherine M., and Luttun, Aernout

Subjects
Polymerase chain reaction -- Usage, Polymerase chain reaction -- Methods, Polymerase chain reaction -- Research, Muscles -- Genetic aspects, Muscles -- Research, Peripheral vascular diseases -- Genetic aspects, Peripheral vascular diseases -- Diagnosis, Peripheral vascular diseases -- Research
Abstract

Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients., Introduction Peripheral vascular disease (PVD) is a growing health problem in Western societies. PVD presents itself with different degrees of severity, e.g., intermittent claudication (IC) is an early moderate manifestation [...]

Published
2008

35. Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells

Author

Ross, Jeffrey J., Hong, Zhigang, Willenbring, Ben, Zeng, Lepeng, Isenberg, Brett, Lee, Eu Han, Reyes, Morayma, Keirstead, Susan A., Weir, E. Kenneth, Tranquillo, Robert T., and Verfaillie, Catherine M.

Subjects
Cytokines -- Research, Smooth muscle -- Research
Abstract

Smooth muscle formation and function are critical in development and postnatal life. Hence, studies aimed at better understanding SMC differentiation are of great importance. Here, we report that multipotent adult [...]

Published
2006

36. Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair

Author

Maes, Christa, Coenegrachts, Lieve, Stockmans, Ingrid, Daci, Evis, Luttun, Aernout, Petryk, Anna, Gopalakrishnan, Rajaram, Moermans, Karen, Smets, Nico, Verfaillie, Catherine M., Carmeliet, Peter, Bouillon, Roger, and Carmeliet, Geert

Subjects
Fracture fixation -- Research, Cartilage cells -- Research, Bone regeneration -- Research
Abstract

Current therapies for delayed- or nonunion bone fractures are still largely ineffective. Previous studies indicated that the VEGF homolog placental growth factor (PlGF) has a more significant role in disease [...]

Published
2006

37. Characterization of expanded intermediate cell mass in zebrafish chordin morphant embryos

Author

Leung, Anskar Y.H., Mendenhall, Eric M., Kwan, Tommy T.F., Liang, Raymond, Eckfeldt, Craig, Chen, Eleanor, Hammerschmidt, Matthias, Grindley, Suzanne, Ekker, Stephen C., and Verfaillie, Catherine M.

Subjects
Zebra fish -- Research, Gene expression -- Research, Biological sciences
Abstract

We investigated the mechanisms of intermediate cell mass (ICM) expansion in zebrafish chordin (Chd) morphant embryos and examined the role of BMPs in relation to this phenotype. At 24 h post-fertilization (hpf), the expanded ICM of embryos injected with chd morpholino (MO) ([Chd.sup.Mo] embryos) contained a monotonous population of hematopoietic progenitors. In situ hybridization showed that hematopoietic transcription factors were ubiquitously expressed in the ICM whereas vascular gene expression was confined to the periphery. BMP4 (but not BMP2b or 7) and smad5 mRNA were ectopically expressed in the [Chd.sup.MO] ICM. At 48 hpf, monocytic cells were evident in both the ICM and circulation of [Chd.sup.MO] but not WT embryos. While injection of BMP4 MO had no effect on WT hematopoiesis, co-injecting BMP4 with chd MOs significantly reduced ICM expansion. Microarray studies revealed a number of genes that were differentially expressed in [Chd.sup.Mo] and WT embryos and their roles in hematopoiesis has yet to be determined. In conclusion, the expanded ICM in [Chd.sup.MO] embryos represented an expansion of embryonic hematopoiesis that was skewed towards a monocytic lineage. BMP4, but not BMP2b or 7, was involved in this process. The results provide ground for further research into the mechanisms of embryonic hematopoietic cell expansion. Keywords: Zebrafish; Chordin; BMP; Morpholino; Hematopoiesis; Gene expression; Microarray; Differentiation

Published
2005

41. Public stem cell banks: considerations of justice in stem cell research and therapy

Author

Faden, Ruth R., Dawson, Liza, Bateman-House, Alison S., Agnew, Dawn Mueller, Bok, Hilary, Brock, Dan W., Chakravarti, Aravinda, Gao, Xiao-Jiang, Greene, Mark, Hansen, John A., King, Patricia A., O'Brien, Stephen J., Sachs, David H., Schill, Kathryn E., Siegel, Andrew, Solter, Davor, Suter, Sonia M., Verfaillie, Catherine M., Walters, LeRoy B., and Gearhart, John D.

Subjects
Biological sciences, Health
Abstract

The forthcoming transition in the focus of stem cell research from basic science in the development of therapies raises important questions of justice. This transition is marked by increasing interest [...]

Published
2003

42. MAPC culture conditions support the derivation of cells with nascent hypoblast features from bone marrow and blastocysts

Author

Lo Nigro, Antonio, Geraerts, Martine, Notelaers, Tineke, Roobrouck, Valerie D., Muijtjens, Manja, Eggermont, Kristel, Subramanian, Kartik, Ulloa-Montoya, Fernando, Park, Yonsil, Owens, Jason, Burns, Terry C., Low, Walter, Sharma, Shikha, Sohni, Abhishek, Crabbe, Annelies, Pauwelyn, Karen, Roelandt, Philip, Agirre, Xabier, Prosper, Felipe, OʼBrien, Timothy D., Zwijsen, An, Hu, Wei-Shou, Binas, Bert, and Verfaillie, Catherine M.

Published
2012
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48. Integrative and perturbation-based analysis of the transcriptional dynamics of TGFβ/BMP system components in transition from embryonic stem cells to neural progenitors

Author

Dries, Ruben, primary, Stryjewska, Agata, additional, Coddens, Kathleen, additional, Okawa, Satoshi, additional, Notelaers, Tineke, additional, Birkhoff, Judith, additional, Dekker, Mike, additional, Verfaillie, Catherine M., additional, Sol, Antonio, additional, Mulugeta, Eskeatnaf, additional, Conidi, Andrea, additional, Grosveld, Frank G., additional, and Huylebroeck, Danny, additional

Published
2019
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49. N‐acetylcysteine prevents oxidized low‐density lipoprotein‐induced reduction of MG53 and enhances MG53 protective effect on bone marrow stem cells

Author

Li, Xin, primary, Jiang, Meng, additional, Tan, Tao, additional, Narasimhulu, Chandrakala A., additional, Xiao, Yuan, additional, Hao, Hong, additional, Cui, Yuqi, additional, Zhang, Jia, additional, Liu, Lingjuan, additional, Yang, Chunlin, additional, Li, Yixi, additional, Ma, Jianjie, additional, Verfaillie, Catherine M., additional, Parthasarathy, Sampath, additional, Zhu, Hua, additional, and Liu, Zhenguo, additional

Published
2019
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