Concise Review: Alchemy of Biology: Generating Desired Cell Types from Abundant and Accessible Cells

Abstract

A major goal of regenerative medicine is to produce cells to participate in the generation, maintenance, and repair of tissues that are damaged by disease, aging, or trauma, such that function is restored. The establishment of induced pluripotent stem cells, followed by directed differentiation, offers a powerful strategy for producing patient-specific therapies. Given how laborious and lengthy this process can be, the conversion of somatic cells into lineage-specific stem/progenitor cells in one step, without going back to, or through, a pluripotent stage, has opened up tremendous opportunities for regenerative medicine. However, there are a number of obstacles to overcome before these cells can be widely considered for clinical applications. Here, we focus on induced transdifferentiation strategies to convert mature somatic cells to other mature cell types or progenitors, and we summarize the challenges that need to be met if the potential applications of transdifferentiation technology are to be achieved.

High Runx1 Levels Promote a Reversible, More-Differentiated Cell State in Hair-Follicle Stem Cells during Quiescence

“…De-differentiation can be achieved by nuclear transfer or forced expression of master transcription factors (Pournasr et al, 2011). Germ line transit-amplifying (TA) cells revert to stem cells (SCs) in the adult mouse and fly testis (Simons and Clevers, 2011; Spradling et al, 2011).…”

Exploring the Mechanisms of Differentiation, Dedifferentiation, Reprogramming and Transdifferentiation

“…We can adjust two self activation strength and to be relative larger to force the differentiated cell to a pluripotent cell with higher inhibition strength , and then re-differentiate the pluripotent cell to our target differentiated cell type [24]. This process can be viewed as an initial epigenetic activation phase representing the redifferentiation after a temporal overexpression of pluripotent reprogramming factors to a pluripotent state [4], [24], [49]. Somatic cells can be transdifferentiated by temporal over-expressions of pluripotent reprogramming transcription factors.…”

“…Transdifferentiation can be induced by down regulating the lineage specific marker gene () of the original differentiated cell (decreasing self activation ) while activating another lineage specific marker gene () of the final differentiated cell (increasing self activation ) at relative lower inhibition strength , through an intermediate state or a series of indeterminate states. This process can be viewed as lineage-instructive transcription representing the induction of lineage specific gene for the target differentiated cells [4], [49]. This gives us a new understanding that the topography of underlying potential landscapes in cell development dynamics determines the feasibility and efficiency of cell type switchings.…”

Manufacturing Cell Therapies Using Engineered Biomaterials

“…Multiplexed gene editing is being used to improve chimeric antigen receptor T-cell (CAR-T) therapies by enabling the use of allogenic cells [22], circumventing graft versus host disease [23], CTLA-4 inhibition or PD1 inhibition resistance [24] or combinations thereof, paving the way for much more feasible and effective therapy. Epigenomic transdifferentiation, or the conversion between cell types without passing through an intermediate pluripotent state, is an attractive option for generating desired cell populations while avoiding laborious reprogramming and differentiation processes [25]. This technique may additionally allow access to other healing modes, such as therapeutic transdifferentiation using either implanted cells [26] or small molecules in vivo [27].…”