ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2020 and some content may be unavailable. To unlock all content for 2020, please visit the archives.

Abstract: PO0883

Successful Introduction of Renovascular Units into the Mammalian Kidney

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Pleniceanu, Oren, Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
  • Gnatek, Yehudit, Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
  • Rosenzweig, Barak, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel
  • Eisner, Alon, Assuta Ashdod Hospital, Ashdod, South, Israel
  • Dotan, Zohar A., Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel
  • Fine, Leon G., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Greenberger, Shoshana, Sheba Medical Center at Tel Hashomer, Tel Hashomer, Israel
  • Dekel, Benjamin, Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
Background

Various cell-based therapies, aimed at replenishing renal parenchyma, have been proposed as means to treat chronic kidney disease (CKD). However, a key limitation to the applicability of these strategies is the failure of in-vivo administered cell types to develop donor-derived vessels, resulting in poor graft survival. Similarly, such strategies do not address renal hypoxia, a key factor in CKD progression. We hypothesized that administering self-organizing human renal tubule-forming cells (RTFCs) derived from adult and fetal kidneys, previously shown to exert a functional effect in CKD mice, alongside mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs), would result in generation of both vessels and tubules with potential interaction.

Methods

NOD-SCID mice were injected with either RTFCs or a mix of RTFCs, MSCs and ECFCs in Matrigel into the sub-cutis (SC), under the renal capsule or into the renal parenchyma. The resulting grafts were analyzed after 2 weeks.

Results

While RTFC-derived grafts harbored few host-derived vessels, injection of MSC, ECFCs and RTFCs into the SC, sub-renal capsular space, or renal parenchyma, resulted in robust formation of donor-derived reno-vascular units. These consisted of both well-developed renal tubules tubular epithelia of different nephron segments, and human vascular networks, which connect to host vasculature. The latter demonstrated the presence of both CD31+ endothelium and αSMA+ pericytes, originating from administered ECFCs and MSCs, respectively. Notably, MSC/ECFC-derived vessels augmented in-vivo tubulogenesis by RTFCs while in vitro co-culture experiments showed MSC/ECFCs to induce self-renewal and mesenchymal-epithelial transition-associated genes in RTFCs, disclosing paracrine effects.

Conclusion

Combined cell therapy of vessel-forming cells and RTFCs aimed at enhancing tubulogenesis and potentially alleviating renal hypoxia may serve as the basis for new renal regenerative therapies.