Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration

Anthony L. Mescher

doi:10.1002/reg2.77

De NovoKidney Regeneration with Stem Cells

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/453519 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Shinya Yokote ◽

Shuichiro Yamanaka ◽

Takashi Yokoo

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Tissue Repair ◽

De Novo ◽

Kidney Regeneration ◽

Cell Based Therapy ◽

Organ Regeneration ◽

Promising Therapeutic Approach ◽

Stage Renal Disease ◽

End Stage

Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair andde novowhole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration.

Download Full-text

Exploring the Molecular Crosstalk between Pancreatic Bud and Mesenchyme in Embryogenesis: Novel Signals Involved

International Journal of Molecular Sciences ◽

10.3390/ijms20194900 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4900

Author(s):

Ilaria Guerriero ◽

Maria Teresa De Angelis ◽

Fulvio D’Angelo ◽

Rita Leveque ◽

Eleonora Savignano ◽

...

Keyword(s):

Signaling Pathways ◽

Tissue Repair ◽

Global Gene Expression ◽

Bioinformatic Analysis ◽

Pancreatic Tissue ◽

Organ Regeneration ◽

Multistep Process ◽

Pancreatic Epithelium ◽

Signaling Activation ◽

Pancreatic Embryogenesis

Pancreatic organogenesis is a multistep process that requires the cooperation of several signaling pathways. In this context, the role of pancreatic mesenchyme is important to define the epithelium development; nevertheless, the precise space–temporal signaling activation still needs to be clarified. This study reports a dissection of the pancreatic embryogenesis, highlighting the molecular network surrounding the epithelium–mesenchyme interaction. To investigate this crosstalk, pancreatic epithelium and surrounding mesenchyme, at embryonic day 10.5, were collected through laser capture microdissection (LCM) and characterized based on their global gene expression. We performed a bioinformatic analysis to hypothesize crosstalk interactions, validating the most promising genes and verifying the precise localization of their expression in the compartments, by RNA in situ hybridization (ISH). Our analyses pointed out also the c-Met gene, a very well-known factor involved in stimulating motility, morphogenesis, and organ regeneration. We also highlighted the potential crosstalk between Versican (Vcan) and Syndecan4 (Sdc4) since these genes are involved in pancreatic tissue repair, strengthening the concept that the same signaling pathways required during pancreatic embryogenesis are also involved in tissue repair. This finding leads to novel strategies for obtaining functional pancreatic stem cells for cell replacement therapies.

Download Full-text

Precise let-7 expression levels balance organ regeneration against tumor suppression

eLife ◽

10.7554/elife.09431 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 33

Author(s):

Linwei Wu ◽

Liem H Nguyen ◽

Kejin Zhou ◽

T Yvanka de Soysa ◽

Lin Li ◽

...

Keyword(s):

Liver Cancer ◽

Mouse Models ◽

Liver Damage ◽

Tissue Damage ◽

Tissue Repair ◽

High Dose ◽

Organ Regeneration ◽

Microrna Family ◽

Dose Dependent

The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes. let-7 dependent regeneration phenotypes resulted from influences on the insulin-PI3K-mTOR pathway. We found that chronic high-dose let-7 overexpression caused liver damage and degeneration, paradoxically leading to tumorigenesis. These dose-dependent roles for let-7 in tissue repair and tumorigenesis rationalize the tight regulation of this microRNA in development, and have important implications for let-7 based therapeutics.

Download Full-text