The origin and role of the renal stroma

Development ◽  
2021 ◽  
Vol 148 (19) ◽  
Author(s):  
Sean B. Wilson ◽  
Melissa H. Little

ABSTRACT The postnatal kidney is predominantly composed of nephron epithelia with the interstitial components representing a small proportion of the final organ, except in the diseased state. This is in stark contrast to the developing organ, which arises from the mesoderm and comprises an expansive stromal population with distinct regional gene expression. In many organs, the identity and ultimate function of an epithelium is tightly regulated by the surrounding stroma during development. However, although the presence of a renal stromal stem cell population has been demonstrated, the focus has been on understanding the process of nephrogenesis whereas the role of distinct stromal components during kidney morphogenesis is less clear. In this Review, we consider what is known about the role of the stroma of the developing kidney in nephrogenesis, where these cells come from as well as their heterogeneity, and reflect on how this information may improve human kidney organoid models.

2016 ◽  
Vol 215 (3) ◽  
pp. 401-413 ◽  
Author(s):  
Maryam Yousefi ◽  
Ning Li ◽  
Angela Nakauka-Ddamba ◽  
Shan Wang ◽  
Kimberly Davidow ◽  
...  

Regeneration of the intestinal epithelium is driven by multiple intestinal stem cell (ISC) types, including an active, radiosensitive Wnthigh ISC that fuels turnover during homeostasis and a reserve, radioresistant Wntlow/off ISC capable of generating active Wnthigh ISCs. We examined the role of the Msi family of oncoproteins in the ISC compartment. We demonstrated that Msi proteins are dispensable for normal homeostasis and self-renewal of the active ISC, despite their being highly expressed in these cells. In contrast, Msi proteins are required specifically for activation of reserve ISCs, where Msi activity is both necessary and sufficient to drive exit from quiescence and entry into the cell cycle. Ablation of Msi activity in reserve ISCs rendered the epithelium unable to regenerate in response to injury that ablates the active stem cell compartment. These findings delineate a molecular mechanism governing reserve ISC quiescence and demonstrate a necessity for the activity of this rare stem cell population in intestinal regeneration.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jennifer K Lang ◽  
Rebecca F Young ◽  
Hashmat Ashraf ◽  
John M Canty

Numerous experimental and clinical studies have shown a beneficial effect of cardiosphere-derived cell (CDC) therapy on regeneration of injured myocardium. Paracrine signaling by CDC secreted exosomes is hypothesized to be the principal mediator of improved function, however the mechanism of exosome uptake, cell specificity, and information transfer has yet to be elucidated. Our aim was to define the role of physiologically secreted human CDC-derived exosomes on cardiac fibroblasts, endothelial cells and cardiomyocytes by employing a knockdown (KD) strategy against nSMase2 and Rab27a, two genes crucial in exosome secretion. Methods: Human CDCs (hCDCs) were grown from atrial tissue biopsy explant culture and characterized by flow cytometry and immunocytochemistry. CDC-derived exosomes were isolated and characterized by particle size, immunoblot analysis and electron microscopy. Protein concentration of exosome preparations was quantified by Bradford microassay. nSMase2 and Rab27a shRNAi lentivirus was generated and used to create stable CDC knockdown lines. Co-culture transwell in vitro assays were designed to assess target cell proliferation, migration, angiogenesis, and fibrotic gene expression. Results: hCDCs expressed CD105, CD90, GATA4 and Nkx2.5, and were CD45 and cardiac troponin T negative. hCDC-derived exosomes were immunoreactive for CD63 and HSP90 and negative for Cyctochrome c and EEA1. shRNAi KD of nSMase2 and Rab27a resulted in successful blockade of exosome release from hCDCs. HUVECs co-cultured with scrambled shRNAi CDCs versus shRNAi nSMase2 KD CDCs showed increased angiogenesis and migration without affecting proliferation. While TGF-β stimulation of human cardiac fibroblasts significantly increased collagen I (COLI) and collagen III (COLIII) gene expression, there was no significant decrease in COLI or COLIII after treatment with exosomes. Conclusions: Secretion of hCDC-derived exosomes was effectively inhibited by nSMase2 and Rab27a lentiviral KD. Exosome release contributed to the angiogenic and pro-migratory effects of hCDCs but did not play a role in the fibrotic gene expression of human cardiac fibroblasts, suggesting a role for physiological exosome secretion in stem cell-mediated cardiac repair.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Appalaraju Jaggupilli ◽  
Eyad Elkord

Cancer stem cell population is a subset of cells capable of dictating invasion, metastasis, heterogeneity, and therapeutic resistance in tumours. Eradication of this rare population is a new insight in cancer treatment. However, prospective identification, characterization, and isolation of these CSCs have been a major challenge. Many studies were performed on surface markers for potential identification and isolation of CSCs. Lack of universal expression of surface markers limits their usage and no best combination of markers has yet been confirmed to identify CSCs capable of initiating and metastasizing tumours. CD44, a hyaluronic acid receptor, is one of the most commonly studied surface markers, which is expressed by almost every tumour cell. CD24, a heat stable antigen, is another surface marker expressed in many tumour types. However, their expression and prognostic value in isolating CSCs are still an enduring ambiguity. In this critical review, we assess the role of CD44 and CD24 in tumour initiation, development, and metastasis. We mainly focus on analysing the significance of CD44 and CD24 as CSC surface markers in combination or with other putative markers in different types of cancer.


2011 ◽  
Vol 10 (2) ◽  
pp. 182
Author(s):  
O.G. Ivanovski ◽  
S.K. Saidi ◽  
S.O. Stavridis ◽  
S.A. Dohcev ◽  
O.L. Stankov ◽  
...  

Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 634-645 ◽  
Author(s):  
W. S. Tyler ◽  
Eero Niskanen ◽  
Frederick Stohlman ◽  
Jane Keane ◽  
Donald Edward

Abstract An in vivo diffusion chamber (DC) culture technique was used to evaluate the role of circulating humoral factors in the control of myelopoiesis. Normal mouse bone marrow cell suspensions sealed in DC’s were implanted intraperitoneally into mice or rats rendered neutropenic by pretreatment with cyclophosphamide, and the growth of cells in the DC’s was evaluated at intervals thereafter. When marrow was cultured in hosts with graded neutropenia, a dose-related augmentation of myelopoiesis was demonstrated. The growth of macrophages and of pluripotent stem cells, measured by the spleen colony-forming technique, was also enhanced by culture in neutropenic hosts. These data provide further evidence that the rate of myelopoiesis is influenced by a circulating humoral factor. They further suggest that a humoral or hormonal factor is important in control of the pluripotent stem cell population.


2011 ◽  
Vol 44 (13) ◽  
pp. S308
Author(s):  
Darabi Shahram ◽  
Tiraihi Taki ◽  
Nourizadeh Ali

Sign in / Sign up

Export Citation Format

Share Document