Human pluripotent stem cells (hPSCs) are capable of unlimited proliferation and may give rise to any tissue type in the human body. There are two types of hPSCs - embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). These cells may be used as in vitro models of development and hold enormous potential for regenerative medicine applications. However, there are considerable roadblocks to widespread use of hPSCs, chief among which are complexity and cost. Complexity arises from the difficulty in maintaining pluripotency and directing differentiation into desirable lineages with high efficiency. The cost i due to reliance on expensive recombinant growth factors (GFs) and other reagents used in copious amounts over multiple weeks. We have recently made a fascinating observation that stem cells as well as adult cells cultured inside microfluidic devices without perfusion retained phenotype and function significantly better than cells in standard cultureware. Further investigation revealed that cells inside small volumes of microfluidic chambers were upregulating endogenous GFs. Building on these observations, we propose to develop novel cell culture microsystems that will harness cell-secreted signals for maintenance and differentiation of stem cells. Overall impact: This project aims to shift the paradigm of cell cultre away from reliance on exogenous growth factors and towards harnessing cells' own endogenous signals. This will b
Stem cells have tremendous promise as a cellular source of tissues or organs in human body. However; stem cells remain difficult to culture due to complex protocols; high cost of reagents and batch-to-batch differences in reagent quality. We propose developing novel tools for culturing stem cells. These novel cell culture systems or microsystems will be designed to elicit cells to produce their own reagents/signals for differentiating into tissues or organs. Reliance on cells' own signals will dramatically reduce cos of cell culture while improving reproducibility and robustness of differentiation protocols.
| Guicciardi, Maria Eugenia; Trussoni, Christy E; Krishnan, Anuradha et al. (2018) Macrophages contribute to the pathogenesis of sclerosing cholangitis in mice. J Hepatol 69:676-686 |
| Son, Kyung Jin; Gheibi, Pantea; Stybayeva, Gulnaz et al. (2017) Detecting cell-secreted growth factors in microfluidic devices using bead-based biosensors. Microsyst Nanoeng 3: |
| Gheibi, Pantea; Son, Kyung Jin; Stybayeva, Gulnaz et al. (2017) Harnessing endogenous signals from hepatocytes using a low volume multi-well plate. Integr Biol (Camb) 9:427-435 |
| Siltanen, Christian; Diakatou, Michalitsa; Lowen, Jeremy et al. (2017) One step fabrication of hydrogel microcapsules with hollow core for assembly and cultivation of hepatocyte spheroids. Acta Biomater 50:428-436 |
| Haque, Amranul; Gheibi, Pantea; Stybayeva, Gulnaz et al. (2016) Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate selection during liver injury. Sci Rep 6:36077 |
