The 488th Veterinary Medicine Seminar "In Vivo Kidney Regeneration with Organ-derived Extracellular Matrix" Speaker: Dr. Kazuki Tajima (Small Animal Internal Medicine Laboratory 2)

2023-06-22
17:00
LECTURE ROOM A31, 3RD FLOOR OF BUILDING A

Event Summary

The 488th Veterinary Seminar will be held as follows

We look forward to seeing many of you there.

The 488th Veterinary Medicine Seminar .

Date] June 22 (Thursday)

VENUE】 A31 LECTURE ROOM, 3RD FLOOR OF BUILDING A

Time】 17:00~

Speaker】 Dr. Kazuki Tajima (Laboratory of Small Animal Science 2)

Title] In Vivo Kidney Regeneration with Organ-derived Extracellular Matrix

Summary

The extracellular matrix is very useful for cellular growth, proliferation, and differentiation. The extracellular matrix is composed of various proteins, and its composition is known to vary from organ to organ, and even from region to region within the same organ. Therefore, it is impossible to artificially reproduce the extracellular matrix of an organ completely with current technology. We have established a method to create organ-specific extracellular matrices using decellularization technology, in which cellular components are removed and only the extracellular matrix is left. This organ-specific extracellular matrix provides an optimal environment for cells in the target organ. In this study, we attempted to regenerate kidneys that do not regenerate in vivo by adding extracellular matrix to the kidneys. As a result, glomerular and tubular structures were regenerated, and functions such as blood flow and urine production were confirmed in the regenerated organ. This study suggests that even non-regenerated organs can be regenerated with the optimal extracellular matrix.

Reasons for selection

Among the papers published by faculty members of the Department of Veterinary Medicine as first or corresponding authors during the period from January to December 2022, the Seminar Committee has selected the paper by Dr. Tajima et al. as the Best Paper 2022 for the following reasons.

Tajima K. et al., NPJ Regen. Med. 2022

An organ-derived extracellular matrix triggers in situ kidney regeneration in a preclinical model

https://www.nature.com/articles/s41536-022-00213-y

The paper shows that cells derived from pig kidneys were transplanted into a matrix on the surface of a partially resected kidney and showed regeneration of nephrons and blood flow.

We felt that this was very valuable data obtained using animal models in the advanced field of regenerative medicine.

The study demonstrated that a sterile, cell-free (decellularized?) kidney harvested from a pig can regain function when transplanted into a partially resected kidney. The study demonstrates that a cell-free (decellularized?) kidney can regain function when transplanted into a partially resected kidney. The cell-free and functional recovery after transplantation is demonstrated by assessing histochemistry, expression of relevant genes, biomarkers, and clinical approaches. The appropriateness of the approach and the function of the transplanted kidney have been demonstrated using a human-like model, the pig, and strongly suggest success in the field of transplantation.

When a decellularized kidney is transplanted into a partially resected kidney, it is shown that blood supply and glomeruli and tubules are formed within the Matrix, and I felt that this is an important study that will contribute to the development of regenerative medicine. I felt that this is an important research that will contribute to the development of regenerative medicine. I felt that further development is expected in this paper to see to what extent renal function can be restored and to what scale of resection it can be tolerated.

THE PAPER REPORTED THAT DECELLULARIZED PORCINE EXTRACELLULAR MATRIX (ECM), SUTURED AND TRANSPLANTED INTO A PARTIALLY RESECTED KIDNEY, REGENERATES THE KIDNEY STRUCTURE BASED ON THE TRANSPLANTED ECM WITHOUT FIBROSIS.

The data suggest that the self-healing ability of the matrix can induce structural and functional regeneration of damaged organs.

PERSONALLY, ALTHOUGH BLOOD FLOW WAS CONFIRMED IN THE KIDNEYS THAT HAD BEEN SYSTEMATICALLY RESTORED BY ECM TRANSPLANTATION, I WOULD HAVE LIKED TO HEAR MORE ABOUT THE EXTENT TO WHICH RENAL FUNCTION HAD BEEN RESTORED, THE EXTENT TO WHICH NORMAL KIDNEYS COULD BE SYSTEMATICALLY RESTORED IF THEY REMAINED INTACT, AND HOW THE COMPOSITION OF THE ECM THAT SERVES AS THE SCAFFOLD FOR GLOMERULI, TUBULES, AND OTHER STRUCTURES DIFFERS. I WOULD LIKE TO HEAR MORE IN DEPTH ABOUT THE DIFFERENCES IN THE COMPOSITION OF THE ECM, WHICH IS THE SCAFFOLD FOR GLOMERULI, TUBULES, AND OTHER STRUCTURES (AND HOW DIFFERENTIATED CELLS ARE INDUCED BY THESE DIFFERENCES).

This is an important study that showed that the kidney cells that make up the kidney regenerate in transplanted decellularized kidneys. This was a difficult and demanding work from a procedural point of view because of the large number of data in this candidate paper and the fact that the transplantation experiments were performed using pigs. However, we felt that the study was in a preliminary stage due to the lack of functional analysis and the weak conduction of blood flow and urinary drainage pathways.

As stated in the Methods, this is basically an experiment conducted at Keio University, so it is somewhat difficult to rank it as the best paper from Kitasato University and School of Veterinary Medicine. Therefore, we do not rank them.

 The paper demonstrated that transplantation of decellularized kidneys into partially resected kidneys in pigs can increase cellularity and make the kidneys functional. The paper showed similar results in rats, and there are similar reports in other organs as well. This is a milestone in terms of human medicine.

This paper demonstrates that transplantation of decellularized extracellular matrix derived from kidneys into pig kidneys induces renal regeneration within the extracellular matrix.

In the field of high impact renal regenerative medicine, I think this paper is very valuable for its in vivo evaluation of extracellular matrix transplantation. I am also interested to see how this can be connected to the evaluation of renal function.

We recommend this paper as a candidate for best paper based on its impact and future development potential.

This paper demonstrates morphologically and functionally that kidney-derived extracellular matrix induces renal regeneration using a partial kidney resection model in pigs. I felt that this paper has a great impact in that it provides a new option for the treatment of renal diseases, different from dialysis and kidney transplantation, and shows the efficacy of such organ-derived extracellular matrix in organ regeneration using pigs. All of the other candidate papers were excellent, but I ranked this paper first because I felt that it had the greatest impact from the experimental method to the results.

This research is related to a new technology for nephron regeneration in kidneys, which is highly expected to be applied in medicine and veterinary medicine. as a more human-like model, and demonstrates the regeneration of nephrons by transplantation of extracellular matrix derived from porcine kidney. This is a cutting-edge technology that sheds light on the treatment of kidney failure, which has become an important issue in both the medical and veterinary fields, and has a very strong impact.

Although I could not understand the differences in the tissue images in the photographs shown and was concerned about the extent of Kitasato University's contribution, the paper seemed to make a significant contribution to the fields of organ transplantation and regenerative medicine, including regeneration of kidney tissue using kidney-derived extracellular matrix and its application to clinical practice.

This study shows that renal nephrons, which were previously thought to be non-regenerative organs, can be regenerated inside the decellularized renal skeleton. The fact that the renal skeleton contains various signaling molecules that induce self-renewal and repair is very interesting, and further elucidation of the mechanism is expected.

I thought the paper showed the application of extracellular matrix to regenerative medicine, and I thought the research was of great significance not only in the veterinary field but also in the medical field.

As a preclinical model for regenerative medicine, kidneys were decellularized in pigs, the structures were transplanted, and renal regeneration was observed. Functional nephron regeneration was induced, making this a very impactful study.

Both the volume of data and the level of journals in which they are published are high. It is not difficult to imagine that the journal will attract widespread interest in veterinary medicine in terms of regenerative medicine research.

It is interesting to clarify the regeneration of nephrons. I have the impression that there will be a lot of questions and active discussions on various tips on how to create a temperament for regeneration.

Paper on kidney regeneration in pigs using decellularized kidneys. The paper presents new findings on the regeneration of kidneys that are thought to be non-regenerative.