Direct reprogramming and biomaterials for controlling cell fate

Abstract

Direct reprogramming which changes the fate of matured cell is a very useful technique with a great interest recently. This approach can eliminate the drawbacks of direct usage of stem cells and allow the patient specific treatment in regenerative medicine. Overexpression of diverse factors such as general reprogramming factors or lineage specific transcription factors can change the fate of already differentiated cells. On the other hand, biomaterials can provide physical and topographical cues or biochemical cues on cells, which can dictate or significantly affect the differentiation of stem cells. The role of biomaterials on direct reprogramming has not been elucidated much, but will be potentially significant to improve the efficiency or specificity of direct reprogramming. In this review, the strategies for general direct reprogramming and biomaterials-guided stem cell differentiation are summarized with the addition of the up-to-date progress on biomaterials for direct reprogramming.

Integrating Biomaterials and Genome Editing Approaches to Advance Biomedical Science

“…High-throughput screening of various material formulations with varied stiffness, degradability, extracellular matrix protein presentation, and soluble factors in this 3D system identified a material formulation that was four times more efficient at generating Oct4 + reprogrammed colonies when compared to the same reprogramming on 2D culture. Similarly, several transdifferentiation protocols for converting fibroblasts directly to a differentiated cell type of interest leverage different biomaterial platforms to boost reprogramming efficiency (202)(203)(204). This reprogramming is likely increased in part by changes in chromatin mobility and protein localization in different material contexts, as mentioned above.…”

The Role of Stiffness in Cell Reprogramming: A Potential Role for Biomaterials in Inducing Tissue Regeneration

“…Reprogramming process needs to be accurately monitored and regulated, otherwise if the process in not sufficiently supervised, the cure might lead to teratoma, and not to the treatment for the patient. In this context there are many biomaterials that can support and cooperate in the reprogramming process, in fact biomaterials are able to supply microenvironments that simulate the exact cell compartment, favoring cell differentiation toward specific cell types [140]. An intensive examination of the bidirectional interplay between cells and compartments is fundamental to engineer next-generation biomaterials, in order to properly direct cell reprogramming in expected behavior.…”

“…Since this discovery, direct reprogramming has come out as a new and important process to manage cell fate, in fact overexpression of several factors, i.e., general reprogramming factors or lineage-specific transcription factors, are responsible for the cell fate change of already differentiated cells. Contextually, biomaterials are able to supply biochemical signals or physical and topographical stimuli on cells, that can guide and influence the cell fate reprogramming [140]. More in-depth, biochemical signals such as ECM components, growth factors, and other molecules are essential for the control of cell fate and reprogramming, through the activation of integrins and other downstream signaling mechanisms [142].…”

Reprogramming cell fate with artificial transcription factors

“…Recently, TFs have been used in a variety of contexts to obtain a number of desired cell states . Perhaps this should not come as a surprise, given the integral role of TFs in regulating cell fates during development.…”