A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration

Abstract

Cellular senescence is a major hurdle for primary cell-based tissue engineering and regenerative medicine. Telomere erosion, oxidative stress, the expression of oncogenes and the loss of tumor suppressor genes all may account for the cellular senescence process with the involvement of various signaling pathways. To establish immortalized cell lines for research and clinical use, strategies have been applied including internal genomic or external matrix microenvironment modification. Considering the potential risks of malignant transformation and tumorigenesis of genetic manipulation, environmental modification methods, especially the decellularized cell-deposited extracellular matrix (dECM)-based preconditioning strategy, appear to be promising for tissue engineering-aimed cell immortalization. Due to few review articles focusing on this topic, this review provides a summary of cell senescence and immortalization and discusses advantages and limitations of tissue engineering and regeneration with the use of immortalized cells as well as a potential rejuvenation strategy through combination with the dECM approach.

Gene Expression Profile in Immortalized Human Periodontal Ligament Fibroblasts Through hTERT Ectopic Expression: Transcriptome and Bioinformatic Analysis

“…In the study published by Lallier and Spencer (2007), although these populations were considered similar, they differed in their expression of roughly 3,240 genes (6% of total analyzed). Thus, considering only the gene numbers, the hTERT immortalization protocol performed by us did not generate profound gene modifications ,which is in agreement with the observations of low phenotypic and karyotypic changes of this protocol compared with a virus protocol, such as SV40 (Wang et al, 2019).…”

“…Another important upregulated gene in hPLF-hTERT was beta-defensin 2 (DEFB4A). Two of several different pathways of gene activation were observed in the immortalized cell line: NOD-2-dependent NF-kβ activation (Wang et al, 2019). Crucial in the innate immune response (Saxena and Yeretssian, 2014), the NOD-like receptors (NLRs) in signaling pathways are transmembrane receptors that show various FIGURE 7 | Graph representing KEGG pathways associated with the differentially expressed genes in hPLF after immortalization processes and their respective number of genes found in the transcriptome analysis.…”

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells

“…Wnt/β-catenin signaling pathway being actively involved in BMSCs differentiation also participates in inducing senescence through interacting with p53/p21 pathway to produce ROS [93]. Moreover, other signaling pathways including MAPK, PI3K/AKT/mTOR, Notch, FGFs and Hipo have been reported to play a crucial role in causing senescence in BMSCs as well [94] (Table 2). BMP, bone morphogenic protein; Wnt, wingless-type MMTV integration site; NELL-1, Neural epidermal growth factor-like (NEL)-like protein 1; FGFs, fibroblast growth factor; IGF-I, insulin-like growth factor-I.…”

TMEM63C, a Potential Novel Target for Albuminuria Development, Is Regulated by MicroRNA-564 and Transforming Growth Factor beta in Human Renal Cells

“…However, the effects of TMEM63C on EMT have not yet been clarified and should be investigated in further experiments. These experiments may include in vivo studies or at least studies in primary kidney cells, since experiments in immortalized cell lines, although important for mechanistic studies, should be viewed with some caution due to a potential permissive oncogenic phenotype for EMT studies [35]. Moreover, the role of EMT per se in the context of renal fibrosis has been questioned [36] and has been a matter of controversy [37].…”