Periodic Reporting for period 1 - NEOGRAFT (NEONATAL KIDNEY STEM PROGENITOR CELLS AS A NOVEL TYPE OF CELL THERAPY)
Periodo di rendicontazione: 2023-01-01 al 2025-06-30
Tackling Kidney Disease with a New Stem Cell Therapy
Chronic kidney disease (CKD) is a major global health issue, causing more than 1.2 million deaths every year. For people with end-stage kidney disease (ESKD), a kidney transplant is the best treatment. However, there is a severe shortage of donor kidneys, creating a huge burden for both individuals and society. By 2030, an estimated 5.4 million people worldwide will need a kidney transplant, but only one in four will receive one. The rest will have to rely on dialysis, a treatment with serious health risks—half of the patients on dialysis do not survive beyond five years.
To address this crisis, our team has discovered a new source of kidney stem cells. We have successfully isolated these cells non-invasively from the urine of premature newborns. We call them neonatal kidney stem/progenitor cells (nKSPCs). These cells come from a stage in kidney development that allows them to grow into different types of kidney cells. They also have the potential to help regulate the immune system and repair damaged kidney tissue.
The NEOGRAFT project is focused on developing a new type of cell therapy for kidney disease.
Our approach involves two key steps:
1. Understanding nKSPCs – We analyze these stem cells from babies of different gestational ages to understand their genetic makeup, immune properties, and ability to repair kidneys. This will help us determine the most effective cell types for therapy.
2. Testing nKSPCs for therapy – We will test these cells in damaged human kidneys that were donated for research but were not suitable for transplantation. By applying the cells to injured kidney tissue, we aim to repair damage and improve kidney function, potentially increasing the number of usable donor organs.
By unlocking the regenerative power of nKSPCs, the NEOGRAFT project is paving the way for a groundbreaking treatment that could change the future of kidney care and offer new hope to millions of patients worldwide.
Chronic kidney disease (CKD) is a major global health issue, causing more than 1.2 million deaths every year. For people with end-stage kidney disease (ESKD), a kidney transplant is the best treatment. However, there is a severe shortage of donor kidneys, creating a huge burden for both individuals and society. By 2030, an estimated 5.4 million people worldwide will need a kidney transplant, but only one in four will receive one. The rest will have to rely on dialysis, a treatment with serious health risks—half of the patients on dialysis do not survive beyond five years.
To address this crisis, our team has discovered a new source of kidney stem cells. We have successfully isolated these cells non-invasively from the urine of premature newborns. We call them neonatal kidney stem/progenitor cells (nKSPCs). These cells come from a stage in kidney development that allows them to grow into different types of kidney cells. They also have the potential to help regulate the immune system and repair damaged kidney tissue.
The NEOGRAFT project is focused on developing a new type of cell therapy for kidney disease.
Our approach involves two key steps:
1. Understanding nKSPCs – We analyze these stem cells from babies of different gestational ages to understand their genetic makeup, immune properties, and ability to repair kidneys. This will help us determine the most effective cell types for therapy.
2. Testing nKSPCs for therapy – We will test these cells in damaged human kidneys that were donated for research but were not suitable for transplantation. By applying the cells to injured kidney tissue, we aim to repair damage and improve kidney function, potentially increasing the number of usable donor organs.
By unlocking the regenerative power of nKSPCs, the NEOGRAFT project is paving the way for a groundbreaking treatment that could change the future of kidney care and offer new hope to millions of patients worldwide.
At NEOGRAFT, my team focuses on gaining a deep understanding of the regenerative potential, immunomodulatory properties, and safety of nKSPC using advanced technologies. Our ultimate goal is to develop a clinical-grade nKSPC suitable for clinical trials.
1. Establishing a Biobank of nKSPCs
We have established a biobank of neonatal kidney stem/progenitor cells (nKSPCs) by collecting and preserving more than 230 cell lines from the urine of 58 premature babies of different gestational ages. Through advanced genetic analysis, we discovered that even cells from the same baby can be quite different. Some had strong kidney stem cell properties, while others—especially from full-term babies—showed a mix of stem cell and more mature kidney cell traits.
2. Harnessing nKSPC Healing Power
- Controlling Inflammation and Preventing Damage
Our in vitro studies demonstrated that nKSPCs can decrease immune cell activation, reducing harmful inflammation and preventing cell death. This could be crucial for protecting kidneys from injury and disease.
- Integrating into Kidney Tissue
To test their regenerative potential, we introduced nKSPCs into mini-kidneys grown in the lab (kidney organoids). The results are promising—these cells successfully integrated into kidney structures, further supporting their potential to repair and restore damaged
kidneys.
3. Testing nKSPCs in Donor Kidneys
To see how nKSPCs could help real human kidneys, we tested them using human donor kidneys that were not suitable for transplantation. We used a technique called machine perfusion, which keeps the kidneys functioning outside the body.
Each experiment involved a pair of kidneys from the same donor—one was treated with nKSPCs, while the other acted as a control, receiving only a standard solution. Over a 28-hour period, the kidneys treated with nKSPCs showed significant improvements:
- Better oxygen use
- Improved blood flow
- Increased urine production
- Lower levels of injury markers
Altogether, these results suggest that donor kidneys treated with nKSPCs experience enhanced metabolism and reduced tissue damage, potentially improving their viability for transplantation.
4. Preparing nKSPCs for Clinical Use
A key step in the NEOGRAFT project is ensuring that nKSPCs can be safely used in future treatments. To achieve this, we developed a specialized, animal-free cell culture medium that allows these cells to grow under conditions that meet the highest safety and quality standards (cGMP).
Using advanced robotics and AI, we tested and optimized this new medium, confirming that it successfully supports nKSPCs’ growth and function while maintaining their regenerative properties.
The next steps will focus on:
- Studying how these cells interact with the immune system
- Further testing their ability to improve kidney function
- Ensuring their safety profile for future clinical applications
1. Establishing a Biobank of nKSPCs
We have established a biobank of neonatal kidney stem/progenitor cells (nKSPCs) by collecting and preserving more than 230 cell lines from the urine of 58 premature babies of different gestational ages. Through advanced genetic analysis, we discovered that even cells from the same baby can be quite different. Some had strong kidney stem cell properties, while others—especially from full-term babies—showed a mix of stem cell and more mature kidney cell traits.
2. Harnessing nKSPC Healing Power
- Controlling Inflammation and Preventing Damage
Our in vitro studies demonstrated that nKSPCs can decrease immune cell activation, reducing harmful inflammation and preventing cell death. This could be crucial for protecting kidneys from injury and disease.
- Integrating into Kidney Tissue
To test their regenerative potential, we introduced nKSPCs into mini-kidneys grown in the lab (kidney organoids). The results are promising—these cells successfully integrated into kidney structures, further supporting their potential to repair and restore damaged
kidneys.
3. Testing nKSPCs in Donor Kidneys
To see how nKSPCs could help real human kidneys, we tested them using human donor kidneys that were not suitable for transplantation. We used a technique called machine perfusion, which keeps the kidneys functioning outside the body.
Each experiment involved a pair of kidneys from the same donor—one was treated with nKSPCs, while the other acted as a control, receiving only a standard solution. Over a 28-hour period, the kidneys treated with nKSPCs showed significant improvements:
- Better oxygen use
- Improved blood flow
- Increased urine production
- Lower levels of injury markers
Altogether, these results suggest that donor kidneys treated with nKSPCs experience enhanced metabolism and reduced tissue damage, potentially improving their viability for transplantation.
4. Preparing nKSPCs for Clinical Use
A key step in the NEOGRAFT project is ensuring that nKSPCs can be safely used in future treatments. To achieve this, we developed a specialized, animal-free cell culture medium that allows these cells to grow under conditions that meet the highest safety and quality standards (cGMP).
Using advanced robotics and AI, we tested and optimized this new medium, confirming that it successfully supports nKSPCs’ growth and function while maintaining their regenerative properties.
The next steps will focus on:
- Studying how these cells interact with the immune system
- Further testing their ability to improve kidney function
- Ensuring their safety profile for future clinical applications
The aim of NEOGRAFT project is to establish a novel type of kidney-targeted cell therapy using neonatal kidney stem cells.
Our key achievements:
1. Non-Invasive Stem Cell Collection: We successfully developed a completely non-invasive method to isolate and expand kidney stem cells by collecting urine from preterm babies using a simple gauze in their diaper. This painless and risk-free technique provides a valuable source of stem cells without harming the donors.
2. Establishment of a Large Biobank: We have built a comprehensive biobank of 230 kidney stem/progenitor cell lines, stored at the PipiBank in Amsterdam UMC. This valuable resource supports ongoing research and the future development of kidney regenerative therapies.
3. Development of a Safe, Xeno-Free Culture Medium: To ensure nKSPCs are suitable for clinical use, we created a xeno-free and serum-free cell culture medium that meets clinical-grade standards. This breakthrough will be important for safe large-scale production of nKSPCs for potential future treatments.
4. Demonstration of Functional Benefits in Human Kidneys: Using an ex vivo model with paired human donor kidneys, we found that nKSPCs improved kidney function, increased urine production, and enhanced oxygen consumption. These results suggest that treated kidneys operate in a healthier metabolic state and may be more viable for transplantation.
Next Steps: Bringing nKSPC Therapy to Patients:
To turn these promising findings into real-world treatments, several critical steps must be taken:
- Further Preclinical Studies – Additional research is needed to confirm the safety, effectiveness, and mechanisms by which nKSPCs repair damaged kidneys.
- Clinical Trial Development – Experts estimate that nKSPCs are currently at a Technology Readiness Level (TRL) of 3, meaning further development is required before human trials.
- Setting Clinical Standards – Establishing strict quality control, safety, and ethical guidelines is essential for the responsible translation of stem cell-based kidney therapies.
- Scaling Up for Large-Scale Trials & Commercialization – Support from research institutions, biotech companies, and healthcare organizations is crucial to develop manufacturing capabilities and ensure long-term success.
- Global Collaborations – Partnering with international researchers, biotech firms, and healthcare providers will accelerate the development of nKSPC therapies, making this revolutionary treatment accessible to patients worldwide.
Our key achievements:
1. Non-Invasive Stem Cell Collection: We successfully developed a completely non-invasive method to isolate and expand kidney stem cells by collecting urine from preterm babies using a simple gauze in their diaper. This painless and risk-free technique provides a valuable source of stem cells without harming the donors.
2. Establishment of a Large Biobank: We have built a comprehensive biobank of 230 kidney stem/progenitor cell lines, stored at the PipiBank in Amsterdam UMC. This valuable resource supports ongoing research and the future development of kidney regenerative therapies.
3. Development of a Safe, Xeno-Free Culture Medium: To ensure nKSPCs are suitable for clinical use, we created a xeno-free and serum-free cell culture medium that meets clinical-grade standards. This breakthrough will be important for safe large-scale production of nKSPCs for potential future treatments.
4. Demonstration of Functional Benefits in Human Kidneys: Using an ex vivo model with paired human donor kidneys, we found that nKSPCs improved kidney function, increased urine production, and enhanced oxygen consumption. These results suggest that treated kidneys operate in a healthier metabolic state and may be more viable for transplantation.
Next Steps: Bringing nKSPC Therapy to Patients:
To turn these promising findings into real-world treatments, several critical steps must be taken:
- Further Preclinical Studies – Additional research is needed to confirm the safety, effectiveness, and mechanisms by which nKSPCs repair damaged kidneys.
- Clinical Trial Development – Experts estimate that nKSPCs are currently at a Technology Readiness Level (TRL) of 3, meaning further development is required before human trials.
- Setting Clinical Standards – Establishing strict quality control, safety, and ethical guidelines is essential for the responsible translation of stem cell-based kidney therapies.
- Scaling Up for Large-Scale Trials & Commercialization – Support from research institutions, biotech companies, and healthcare organizations is crucial to develop manufacturing capabilities and ensure long-term success.
- Global Collaborations – Partnering with international researchers, biotech firms, and healthcare providers will accelerate the development of nKSPC therapies, making this revolutionary treatment accessible to patients worldwide.