Renal progenitor organoids have been proposed as a source of tissue for kidney regeneration; however, their clinical translatability has not been demonstrated due to an inability to mass-produce comprehensive renal progenitor organoids and the lack of an effective intra-renal delivery platform that facilitates rapid integration into functionally meaningful sites. This study addresses these shortcomings. Human-induced pluripotent stem cells were differentiated into renal progenitor cells using an established protocol and aggregated using a novel assembly method to produce high yields of organoids. Organoids were encapsulated in collagen-based scaffolds for in vitro study and in vivo implantation into mouse renal cortex. In vitro, the organoids demonstrated sustained cell viability and renal structure maturation over time. In vivo delivered organoids showed rapid integration into host renal parenchyma while showing tubular and glomerular-like structure development and maturity markers. This proof-of-concept study presents many promising results, providing a system of renal organoid formation and delivery that may support the development of clinically translatable therapies and the advancement of in vitro renal organoid studies.

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP59)1 May 2024MP59-05 NEURAL CELL INTEGRATION INTO 3D BIOPRINTED MUSCLE CONSTRUCTS FOR THE RESTORATION OF MUSCLE FUNCTION Ji Hyun Kim, Young-Joon Seol, In Kap Ko, Ickhee Kim, John D. Jackson, James Yoo, Sang Jin Lee, and Anthony Atala Ji Hyun KimJi Hyun Kim , Young-Joon SeolYoung-Joon Seol , In Kap KoIn Kap Ko , Ickhee KimIckhee Kim , John D. JacksonJohn D. Jackson , James YooJames Yoo , Sang Jin LeeSang Jin Lee , and Anthony AtalaAnthony Atala View All Author Informationhttps://doi.org/10.1097/01.JU.0001009476.18935.3b.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bioengineered muscle tissue can be a promising solution to achieve functional recovery of muscle tissue loss. However, conventional fabrication methods are limited to building volumetric tissues with the functional cellular organization. More importantly, bioengineered muscle tissues need to be integrated with the host nervous system following implantation, as a failure of innervation results in muscle tissue atrophy. In this study, we fabricated 3-dimensional (3D) human neural muscle constructs with pre-formed neuromuscular junctions (NMJs) and investigated the feasibility of improving the structural and functional recovery of muscle tissue damage. METHODS: We utilized the 3D bioprinting strategy to fabricate volumetric skeletal muscle constructs that mimic native skeletal muscle organization. To facilitate long-term tissue survival and accelerate neural integration, human neural stem cells (hNSCs) were combined with human muscle progenitor cells (hMPCs) in the 3D bioprinted muscle constructs. To determine the feasibility of treating critical-sized muscle tissue damage, we applied the bioprinted human neural skeletal muscle constructs in a rat model of volumetric muscle loss and evaluated the functional outcomes of muscle tissue reconstruction and innervation. RESULTS: Neural input on the bioprinted muscle construct showed improved muscle differentiation, long-term survival, and formation of NMJs in vitro. Implantation of the bioprinted neural muscle constructs in a rat tibialis anterior (TA) muscle excisional model facilitated rapid innervation and matured into organized muscle tissue that restored normal muscle weight and function. CONCLUSIONS: Our results demonstrate that the creation of innervated bioengineered muscle tissue constructs using the 3D bioprinting system is feasible and that the muscle construct can contribute to the restoration of muscle functions. Source of Funding: This work was supported by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort under Award No. W81XWH-14-2-0004. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e958 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ji Hyun Kim More articles by this author Young-Joon Seol More articles by this author In Kap Ko More articles by this author Ickhee Kim More articles by this author John D. Jackson More articles by this author James Yoo More articles by this author Sang Jin Lee More articles by this author Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023PD31-10 PRODUCTION OF VASCULARIZED FUNCTIONAL ORGAN CONSTRUCTS WITH LONG-TERM SURVIVAL Kelsey Willson, Sang Jin Lee, Young-Wook Moon, John Jackson, Colin Bishop, James Yoo, and Anthony Atala Kelsey WillsonKelsey Willson More articles by this author , Sang Jin LeeSang Jin Lee More articles by this author , Young-Wook MoonYoung-Wook Moon More articles by this author , John JacksonJohn Jackson More articles by this author , Colin BishopColin Bishop More articles by this author , James YooJames Yoo More articles by this author , and Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003324.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Developing large vascularized tissue constructs that can maintain long-term is an ongoing challenge. A strategy that has been gaining much attention is to bioengineer prevascularize tissue constructs that allow for immediate perfusion. We present the development of a large vascularized functional human liver construct that can be maintained for 30 days with high viability METHODS: Vascularized human liver tissue constructs of 1.5 cm in diameter and 6 cm in length were fabricated using an extrusion-based 3D printing system, seeded with hepatocytes (HepG2) in bulk hydrogel (alginate) and human umbilical vein endothelial cells (HUVECs) within the vascular channels. The alginate/HepG2 mixture was placed into a mold. A sacrificial gel (calcium chloride/HUVECs) was used to create vessels. Post printing, the samples were cured using calcium chloride and incubated at 37°C to liquefy the sacrificial gel. The liver tissue constructs were maintained in a media bath for 4 days, followed by media perfusion for 30 days using a peristaltic pump. The tissue samples were removed every 10 days and analyzed for cellular viability and biochemical functionality (albumin/bilirubin production). Immunohistochemistry was used to confirm the location of hepatocytes and endothelial cells. RESULTS: Alginate and calcium chloride was successfully used to fabricate constructs patterned with internal vascular channels running the entire length of the construct. The final constructs were cylindrical and maintained their structural integrity. The liver tissue samples showed high viability following fabrication and maintained a greater than 94 percent viability throughout the 30-day time point. The liver tissue constructs produced albumin and bilirubin at levels comparable to human liver tissue (assayed at 10, 20, and 30 days). In the retrieved constructs endothelial cells were identified on the vascular channel walls surrounded by hepatocytes in the hydrogel. CONCLUSIONS: We have successfully created large vascularized liver tissue constructs patterned with hollow channels using 3D bioprinting. The combination of perfusion and internal channels maintained high viability for 30 days. The liver tissue constructs produced albumin and bilirubin levels comparable to human liver tissue. This is a major step towards creating large vascularized functional liver tissue constructs that could be used for translational applications. Source of Funding: This work is a winner of NASA’s Vascular Tissue Challenge contest. The authors thank NASA for supporting this work in a zero-gravity environment on the International Space Station © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e904 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kelsey Willson More articles by this author Sang Jin Lee More articles by this author Young-Wook Moon More articles by this author John Jackson More articles by this author Colin Bishop More articles by this author James Yoo More articles by this author Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...

Stem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have been proposed as an alternative option for wound care. However, safety and regulatory concerns exist due to the uncharacterized biochemical content and variability across different batches of CM samples. This study presents an alternative treatment strategy to mitigate these concerns by using fully characterized recombinant proteins identified by the CM analysis to promote pro-regenerative healing. This study analyzed the secretome profile generated from human placental stem cell (hPSC) cultures and identified nine predominantly expressed proteins (ANG-1, FGF-7, Follistatin, HGF, IL-6, Insulin, TGFβ-1, uPAR, and VEGF) that are known to contribute to wound healing and angiogenesis. These proteins, referred to as s (CMFs), were used in combination to test the effects on human dermal fibroblasts (HDFs). Our results showed that CMF treatment increased the HDF growth and accelerated cell migration and wound closure, similar to stem cell and CM treatments. In addition, the CMF treatment promoted angiogenesis by enhancing new vessel formation. These findings suggest that the defined CMF identified by the CM proteomic analysis could be an effective therapeutic solution for wound healing applications. Our strategy eliminates the regulatory concerns present with stem cell-derived secretomes and could be developed as an off-the-shelf product for immediate wound care and accelerating healing.

You have accessJournal of UrologyCME1 May 2022MP20-16 CLINICAL TRANSLATION OF ENGINEERED PENILE TISSUE Sita Somara, Teresa Burnette, Namrata Sangha, Lindsey Creahan, Tsghe Abraha, Kathryn Krupp, Tiana Stewart, Torie Westendorf, Brad Damratoski, Lisa Hinshaw, Todd Meinecke, Darren Hickerson, Cynthia Wilkins-Port, Ryan Terlecki, James Yoo, Julie Allickson, Anthony Atala, and John Jackson Sita SomaraSita Somara More articles by this author , Teresa BurnetteTeresa Burnette More articles by this author , Namrata SanghaNamrata Sangha More articles by this author , Lindsey CreahanLindsey Creahan More articles by this author , Tsghe AbrahaTsghe Abraha More articles by this author , Kathryn KruppKathryn Krupp More articles by this author , Tiana StewartTiana Stewart More articles by this author , Torie WestendorfTorie Westendorf More articles by this author , Brad DamratoskiBrad Damratoski More articles by this author , Lisa HinshawLisa Hinshaw More articles by this author , Todd MeineckeTodd Meinecke More articles by this author , Darren HickersonDarren Hickerson More articles by this author , Cynthia Wilkins-PortCynthia Wilkins-Port More articles by this author , Ryan TerleckiRyan Terlecki More articles by this author , James YooJames Yoo More articles by this author , Julie AllicksonJulie Allickson More articles by this author , Anthony AtalaAnthony Atala More articles by this author , and John JacksonJohn Jackson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002553.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Loss or damage of penile tissue due to trauma and disease are life-defining injuries for those affected. Restoration of sexual function is necessary to support recovering psychologically and reestablish the prospect of leading a full and productive life. Recently, the concept of tissue engineering has been proposed to address the goal of restoring normal anatomical tissue configuration and erectile function. METHODS: A penile construct has been engineered by seeding autologous, ex vivo-expanded smooth muscle and endothelial cells seeded onto a naturally derived acellular corporal tissue matrix that possesses the same architecture as native corpora. The proposed clinical indication for the engineered product was for treatment of damaged penile corpora cavernosa. Autologous endothelial cells (EC) and smooth muscle cells (SMC) were isolated from a biopsy obtained from the patient’s cavernosum. Scaffolding was generated by decellularizing a donor penile body. This acellular scaffold was seeded with cells isolated and expanded from the patient’s biopsy. Once seeded, the engineered penile tissue construct was matured in a bioreactor. RESULTS: A robust process, developed in WFIRM RMCC Process Development, is being translated into GMP Manufacturing for the production of a clinical grade engineered penile tissue construct. In-process and release testing procedures have been established for the utilization of autologous cells and decellularized donor scaffold, to deliver a sterile engineered penile tissue final product. Cells were characterized by studying growth kinetics, identity and purity through immunophenotyping and viability assessments. Decellularized scaffolds are evaluated for acellularity through the absence of DNA and cell nuclei. The final product construct has been characterized for cell viability and distribution on the donor scaffold. CONCLUSIONS: Processes for isolating and expanding the cells, decellularization of a donor penile body and production of a final product construct is currently being been optimized and validated to conform to FDA requirements. An investigational New Drug (IND) application for the project has been approved from the Food and Drug Administration (FDA) for carrying out Phase I safety study for this engineered penile tissue product. Source of Funding: This work was supported by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e324 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sita Somara More articles by this author Teresa Burnette More articles by this author Namrata Sangha More articles by this author Lindsey Creahan More articles by this author Tsghe Abraha More articles by this author Kathryn Krupp More articles by this author Tiana Stewart More articles by this author Torie Westendorf More articles by this author Brad Damratoski More articles by this author Lisa Hinshaw More articles by this author Todd Meinecke More articles by this author Darren Hickerson More articles by this author Cynthia Wilkins-Port More articles by this author Ryan Terlecki More articles by this author James Yoo More articles by this author Julie Allickson More articles by this author Anthony Atala More articles by this author John Jackson More articles by this author Expand All Advertisement PDF downloadLoading ...

There is an unprecedented need for new treatments for renal failure, as the incidence of this disease is increasing disproportionately to advancements in therapies. Current treatments are limited by the availability of viable organs, for which there is a worldwide lack. These treatment modalities also require a substantial amount of infrastructure, significantly limiting the access to care in most countries. Kidney tissue engineering approaches promise to develop alternative solutions that address many of the inadequacies in current care. Although many advancements have been made—primarily in the past decade—in biofabrication and whole-organ tissue engineering, many challenges remain. One major hindrance to the progress of current tissue engineering approaches is establishing successful vascularization of developed engineered tissue constructs. This review focuses on the recent advancements that address the vascular challenge, including the biofabrication of vasculature, whole-organ engineering through decellularization and recellularization approaches, microscale organogenesis, and vascularization using organoids in the context of kidney tissue engineering. We also highlight the specific challenges that remain in developing successful strategies capable of clinical translation.

Surgical implantation of biomanufactured skeletal muscle constructs has recently emerged as a promising strategy to treat volumetric muscle defects. However, due to the slow rate of neural regeneration and integration, timely innervation of the implanted constructs with the host peripheral nerves remains an unresolved challenge. This study aims to develop a sustained release neurotrophic factor (NF) delivery system to accelerate peripheral nerve regeneration and innervation of three-dimensional (3D) bioprinted skeletal muscle constructs. Poly (lactic-co-glycolic acid) (PLGA) microspheres were selected as a delivery system for efficient loading and sustained release of two potent NFs: ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF). We demonstrate that the NFs can be loaded within the PLGA microspheres with a high encapsulation efficiency (75.4% ± 12.6%). The NF-loaded microspheres were incorporated into the fibrinogen-based bioink used to produce biomanufactured skeletal muscle constructs and tested for printability. The microspheres did not change the viscoelastic properties of the bioink, nor did they affect the viability of human muscle progenitor cells. The release kinetic test confirmed that the bioprinted muscle constructs with the NFs-loaded microspheres released the NFs in a sustained manner compared to the bioprinted muscle construct without microspheres. The released NFs maintained their biological activities. In an in vitro neurite outgrowth assay, the NFs released from the PLGA microspheres facilitated the neurite growth over a longer time scale than the NFs directly loaded in the hydrogel. These results demonstrate the feasibility of incorporating the microsphere-based NF delivery system for accelerating neural regeneration in future in vivo applications involving biomanufactured muscle constructs.

Chronic Kidney Disease (CKD) is a major medical problem that leads to progressive loss of kidney function in approximately 37 million adults in the United States. Currently, kidney transplantation is the only treatment method that restores renal function; however, the shortage of donor kidneys for transplantation remains a problem. Cell-based therapy provides an alternate approach to augment and restore kidney function. In normal kidneys, dedifferentiation and proliferation of resident tubular epithelial cells are potential mechanisms contributing to repair and regeneration in kidneys with ischemic or chronic disease. We hypothesized that human primary renal cells derived from CKD kidneys could be used to delay the progression of CKD. In a previous study, we demonstrated the feasibility of isolating and expanding renal cells from diseased kidneys and showed that primary renal cells derived from CKD kidneys had similar morphological and functional characteristics to their counterparts from normal healthy kidneys (NK) in vitro. The current study examined the functional and structural effects of CKD derived primary human cells in a rat CKD model. We investigated whether CKD cells are as effective as NK cells for cell therapy. Our results show that primary human renal cells from CKD donors retained their normal phenotypic and functional characteristics, indicating that they could be used for cell therapy to provide functional and morphologic protection from the CKD associated damage in rats by enhancing tubular cell proliferation and reducing apoptosis. These findings suggest that autologous cells obtained from CKD patients could potentially be used for treatments.Funding Information: This study was supported by Tengion Inc. through a sponsored research agreement with Wake Forest Institute for Regenerative Medicine. In addition to supporting the study financially, Tengion Inc. was involved in the study design and progress. This study was supported, in part, by a grant from the State of North Carolina. Declaration of Interests: None declared. Ethics Approval Statement: All procedures were approved by the Wake Forest University School of Medicine Institutional Animal Care and Use Committee.

INTRODUCTION AND OBJECTIVE: Acute kidney injury (AKI) in coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus is much more common than previously thought and is associated with severe disease and high mortality. Despite the fact that the respiratory and immune systems are the main targets of the COVID- 19 virus, AKI is also observed, identi fi ed by the occurrence of proteinuria or hematuria, an increase in serum urea and creatinine levels. The aim of the study is to assess the pathomorphological changes in the kidneys in 100 cases of autopsy of patients with COVID-19 using light microscopy and immunohistochemical diagnostic methods in order to clarify the possible mechanism of AKI. METHODS: The study was carried out using samples obtained from 100 patients, the time interval of the onset of the disease corre- sponded to the 4th wave of the peak of the incidence in Russia (from June 2021). The age of patients varied from 37 to 94 years 72 ( s [ 12.5), men - 34, women - 66. Patients with chronic kidney disease, diabetes mellitus and cancer were not included in the analysis. The cause of death in all cases was acute respiratory failure, histologically de fi ned as diffuse alveolar injury. AKI in accordance with the KDIGO criteria was detected in 34 patients. RESULTS: On light microscopy, diffuse massive damage to the proximal tubules with loss of the brush border, degeneration of vacuoles was detected in 46 patients, massive necrosis of the tubules in 11 patients. In 65 patients, an extremely pronounced congestion of paretic dilated vessels with widespread paravasal hemorrhages was revealed. Paravasal lymphoid in fi ltration of the vascular endothelium was detected in 27 patients. Severe sludge syndrome in small and medium-sized vessels in 46 patients. In almost all cases, hemosiderin granules and hyaline casts were found. The quantitative and qualitative composition of tissue macrophages corresponded to the population data, without visible correlations with the disease. CONCLUSIONS: According to the study, the factors contrib-uting to AKI include systemic hypoxia, abnormal coagulation, increased catabolism due to fever, drug-related rhabdomyolysis or hyperventilation with increased serum degradation products. Thus, our research provides evidence for AKI during the progression of COVID-10. These results contribute to a better understanding of the course and progression of SARS-CoV-2 virus infection. assessed by immuno fl uorescence and functional analysis while mechanisms of action were explored by PCR arrays, Western Blotting and immunostaining. Results were con fi rmed in vitro using podocytes on which C3aR1 was silenced and in vivo using THSD7A induced MN in balb/c mice. RESULTS: Following exposure to sera from MN patients, we have con fi rmed deposition of human lgG on podocytes and formation of MAC complex, accompanied by albumin leakage. MAC inhibition did not prevent albumin leakage while GOAC supplemented with C3aR1 antagonists as well as GOAC using podocytes in which C3aR1 was silenced were able to prevent glomerular fi ltration damage and albumin leakage. Ef fi cacy of C3aR1 antagonists in preventing proteinuria was con fi rmed in vivo, substantiating our fi ndings. CONCLUSIONS: We have successfully developed a glomerulus-on-a-chip system that closely mimics the GFB structure and provides a powerful tool for studying renal regenerative and disease mechanisms in proteinuric diseases. Using a combination of in vitro and in vivo models, we showed that C3a/C3aR signaling plays a dominant role in complement-mediated MN pathogenesis. the cell-based bioprinting due to their capability to inherit the intrinsic cues from native ECM. This study developed a photo-crosslinkable kidney ECM-derived bioink (KdECMMA) that could provide a kidney-speci fi c microenvironment for renal tissue bioprinting. Porcine whole kidneys were decellularized through a perfusion method, dissolved in an acid solution, and chemically modi fi ed by methacrylation. This KdECMMA-based bioink was formulated and evaluated for rheological properties and printability for the printing process. Afterward, the bioprinted cell-laden constructs were implanted in the kidneys of nude rats for subsequent analysis. bioprinted the cortical of showed formed tubular and glomerular-like structures at 1 and 2 months post- surgery. The bioprinted renal constructs exhibited the structural and functional characteristics of the native renal tissue. CONCLUSIONS: We demonstrated the potential of the tissue-speci fi c ECM-derived bioink for cell-based bioprinting that could enhance cellular maturation and eventually tissue formation. 3D bioprinting strategy with kidney-speci fi c ECM bioink has excellent potential to bioengineer a functional renal tissue construct in future regenerative medicine applications. commonly reported with 16 occurrences, followed by II (14), III (9), IV (3) and fi nally I (2). In total, 101 scans were ordered speci fi cally for the evaluation of renal cysts and the Bosniak score was reported on 27 (26.7%) of these studies. Additionally, these scans generated 87 referrals to urology. Of those referred, 67 did not have a Bosniak score reported and 28 were released from urology care after initial consulta-tion. Retrospective review revealed an additional 92 reports where Bosnaik scoring should have been included. CONCLUSIONS: Despite the widespread acceptance of the Bosniak classi fi cation system, it was utilized less than 10% of the time for evaluation of renal cysts at our health system. Limited use of Bos- niak scores on radiology reports and lack of understanding by physi-cians and advance practice providers contributes to increased patient anxiety, unnecessary repeat imaging, and referrals to urology for simple cysts that do not require follow up. We are working with our radiology colleagues to implement a standardized imaging report template to include Bosniak classi fi cation with all renal cysts in order to improve patient care, save hospital resources, and ultimately improve patient outcomes. (Intensive Care Unit) for with (EPN). if CT-imaging METHODS: Analysis of prospectively maintained database of consecutive patients diagnosed clinico-radiologically with EPN from Five scoring systems were evaluated for their predictive ability for the need for ICU management and mortality risk: National Early Warning Score (NEWS), Modi fi ed Early Warning Score (MEWS), ‘ quick' Sequential Organ Failure Assessment score (qSOFA), Systemic In fl ammatory

You have accessJournal of UrologyTransplantation & Vascular Surgery II (PD56)1 May 2024PD56-10 RESTORATION OF KIDNEY FUNCTION IN CHRONIC KIDNEY DISEASE (CKD) USING AUTOLOGOUS HUMAN RENAL CELLS Sunil George, Jennifer Huling, Mehran Abolbashari, Tae Hyoung Kim, Tamer Aboushwareb, John D. Jackson, Anthony Atala, and James Yoo Sunil GeorgeSunil George , Jennifer HulingJennifer Huling , Mehran AbolbashariMehran Abolbashari , Tae Hyoung KimTae Hyoung Kim , Tamer AboushwarebTamer Aboushwareb , John D. JacksonJohn D. Jackson , Anthony AtalaAnthony Atala , and James YooJames Yoo View All Author Informationhttps://doi.org/10.1097/01.JU.0001008928.01012.0d.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Chronic Kidney Disease (CKD) is a major medical problem that leads to progressive loss of kidney function in approximately 37 million adults in the United States. Kidney transplantation is the only treatment that restores renal function; however, a shortage of donor kidneys for transplantation remains a problem. Cell-based therapy may provide an alternative approach to augment and restore kidney function. We hypothesized that human primary renal cells derived from CKD kidneys could reduce CKD progression. This study examined the functional and structural effects of CKD primary cells injected in a rat model of CKD. METHODS: CKD was induced using a model of ischemia-reperfusion. Male Nude (Nu) Rats were anesthetized, and the renal pedicle was obstructed bilaterally for 60 minutes, then released to induce the ischemia-reperfusion injury. Two weeks post-surgery, Gentamycin (100 mg/kg) was injected subcutaneously for five days. Serum creatinine & BUN levels were measured to determine the levels of renal impairment. After inhalational anesthesia, a single dose of Normal Kidney (NK) and (CKD) cells (5x106) suspended in PBS were injected into the upper and lower poles of both kidneys. Controls were injected with saline. Renal function was assessed by measuring serum creatinine (sCr), and blood urea nitrogen (BUN), glomerular filtration rate (GFR) until 12 weeks after cell injection. Histological analyses were applied to evaluate structural damage and regeneration of the chronic kidney. RESULTS: Our results demonstrated that intrarenal injection of NK and CKD cells significantly improved sCr, BUN, and GFR levels throughout the 12-week post-ischemic insult period (p<0.001). Treatment with CKD cells showed a similar improvement in glomerular damage, tubular damage, cell migration, and cell engraftment as the NK cell treatment. Taken together, the work presented here demonstrates the regenerative potential of primary renal CKD cells for the treatment of chronic kidney disease. CONCLUSIONS: Our present study demonstrates that the regenerative efficacy of primary CKD cells and NK cells are similar in terms of phenotypic and functional characteristics. Injection of either cell type showed long-term renal protection, effectively restored the cellular compartments of the host kidney, and improved both paracrine and endocrine functions. These findings clearly demonstrate that culture-expanded renal cells from diseased human kidneys could provide a cell source for an effective cell-based therapy for CKD treatment. Source of Funding: This work was sipported by departmental funds © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1206 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Sunil George More articles by this author Jennifer Huling More articles by this author Mehran Abolbashari More articles by this author Tae Hyoung Kim More articles by this author Tamer Aboushwareb More articles by this author John D. Jackson More articles by this author Anthony Atala More articles by this author James Yoo More articles by this author Expand All Advertisement PDF downloadLoading ...