Daniel Seung Han

All Publications

• Mesenchymal Stem Cells Delivered Locally to Ischemia-Reperfused Kidneys via Injectable Hyaluronic Acid Hydrogels Decrease Extracellular Matrix Remodeling 1 Month after Injury in Male Mice. Cells Han, D. S., Erickson, C., Hansen, K. C., Kirkbride-Romeo, L., He, Z., Rodell, C. B., Soranno, D. E. 2023; 12 (13)

  Abstract

  The translation of stem cell therapies has been hindered by low cell survival and retention rates. Injectable hydrogels enable the site-specific delivery of therapeutic cargo, including cells, to overcome these challenges. We hypothesized that delivery of mesenchymal stem cells (MSC) via shear-thinning and injectable hyaluronic acid (HA) hydrogels would mitigate renal damage following ischemia-reperfusion acute kidney injury. Acute kidney injury (AKI) was induced in mice by bilateral or unilateral ischemia-reperfusion kidney injury. Three days later, mice were treated with MSCs either suspended in media injected intravenously via the tail vein, or injected under the capsule of the left kidney, or MSCs suspended in HA injected under the capsule of the left kidney. Serial measurements of serum and urine biomarkers of renal function and injury, as well as transcutaneous glomerular filtration rate (tGFR) were performed. In vivo optical imaging showed that MSCs localized to both kidneys in a sustained manner after bilateral ischemia and remained within the ipsilateral treated kidney after unilateral ischemic AKI. One month after injury, MSC/HA treatment significantly reduced urinary NGAL compared to controls; it did not significantly reduce markers of fibrosis compared to untreated controls. An analysis of kidney proteomes revealed decreased extracellular matrix remodeling and high overlap with sham proteomes in MSC/HA-treated animals. Hydrogel-assisted MSC delivery shows promise as a therapeutic treatment following acute kidney injury.

  View details for DOI 10.3390/cells12131771

  View details for PubMedID 37443806

• Reply by Authors. The Journal of urology Han, D. S., Walker, J. P., Nicklawsky, A., Boxley, P., Halstead, N. V., Tonzi, M., Hecht, S. L., Staley, A., Eguchi, M., Cockburn, M. G., Roach, J. P., Saltzman, A. F., Cost, N. G. 2023; 209 (3): 590

  View details for DOI 10.1097/JU.0000000000003092.02

  View details for PubMedID 36756967

• Extended Lymph Node Sampling During Surgery for Pediatric Renal Tumors Concerning for Malignancy Does Not Increase Post-Operative Complication Rates. The Journal of urology Walker, J. P., Han, D. S., Nicklawsky, A., Boxley, P., Morrison, J., Tonzi, M., Bruny, J., Roach, J. P., Cost, N. G. 2023: 101097JU0000000000003390

  Abstract

  PURPOSE: Although Children's Oncology Group renal tumor protocols mandate lymph node sampling (LNS) during extirpative surgery for pediatric renal tumors, LNS is often omitted or low yield. Concerns over morbidity associated with extended LNS have led to hesitancy in adopting a formal LNS template. We hypothesized that complications in children undergoing LNS for renal tumors would be rare, and not associated with the number of LNs sampled.METHODS: A single-institution, retrospective review of patients aged 0-18yrs undergoing extirpative renal surgery with LNS for a suspected malignancy between 2005-2019 was performed. Patients with 0 or an unknown number of LNs sampled or <150 days of follow-up were excluded. A "clinically significant" (CS) complication was defined as any Clavien-Dindo complication ≥ III, small bowel obstruction (SBO), chylous ascites, organ injury, or wound infection. The number of LNs sampled and its influence on the odds of experiencing a CS complication was examined.RESULTS: 144 patients met inclusion criteria. Median patient age was 38 months. Twenty-one patients (15%) had a CS complication, the most common of which was ileus/SBO (n = 16). In a multivariable analysis, increased LN yield was not found to influence the odds of experiencing a CS complication (P = .6).CONCLUSIONS: In this cohort, there was no statistically significant difference in CS complications in patients who underwent more extensive LNS during surgery for a suspected malignant pediatric renal tumor. Future studies on protocol adherence, staging accuracy, and survival trends using a LNS template in these patients should be performed.

  View details for DOI 10.1097/JU.0000000000003390

  View details for PubMedID 36821137

• Pediatric Small Renal Masses: Can Tumor Size Predict Histology and the Potential for Nephron-Sparing Surgery? The Journal of urology Han, D. S., Walker, J. P., Nicklawsky, A., Boxley, P., Halstead, N. V., Tonzi, M., Hecht, S. L., Staley, A., Eguchi, M., Cockburn, M. G., Roach, J. P., Saltzman, A. F., Cost, N. G. 2022: 101097JU0000000000003092

  Abstract

  The majority of children with unilateral renal masses (uRM) suspicious for malignancy undergo radical nephrectomy (RN), while nephron-sparing surgery (NSS) is reserved for select cases. We investigated the impact of tumor size (TS) on the probability of histology. We hypothesized that pediatric small renal masses (pSRM) are more likely benign or non-Wilms tumor (WT), thus potentially appropriate for NSS.The Surveillance, Epidemiology, and End Result (SEER) database was analyzed for patients aged 0-18 years diagnosed with a uRM from 2000-2016. Statistical analysis was performed to help determine a TS cut-point to predict WT and assess the predictive value of TS on WT histology. Additionally, a retrospective review was performed of patients 0-18 years old who underwent surgery for a uRM at a single institution from 2005-2019. Statistical analysis was performed to assess the predictive value of TS on final histology.From the SEER analysis, 2,016 patients were included. 1,672 (82.9%) tumors were WT. Analysis revealed 4 cm to be a suitable cut-point to distinguish non-WT. Tumors ≥4 cm were more likely WT (OR 2.67, P≤.001), but this was driven by the statistical significance in children 5-9 years old. From the institutional analysis, 134 patients were included. Ninety-seven (72.3%) tumors were WT. Tumors ≥4 cm had higher odds of being WT (OR 30.85, P = .001), malignant (OR 6.75, P = .005), and of having RN-appropriate histology (OR 46.79, P<.001).The probability that a pediatric uRM is WT increases with TS. Four cm is a logical cut-point to start the conversation around defining pSRMs and may help predict NSS-appropriate histology.

  View details for DOI 10.1097/JU.0000000000003092

  View details for PubMedID 36445021

• Outcomes of dialysis in neonates with anuric end-stage renal disease at birth: ethical considerations. Journal of perinatology : official journal of the California Perinatal Association Han, D. S., Bock, M. E., Glover, J. J., Vemulakonda, V. M. 2022

  Abstract

  INTRODUCTION: We present a case series of neonates with anuric ESRD undergoing renal replacement therapy (RRT) and discuss the associated ethical implications of RRT in this population.METHODS: We reviewed patients who initiated RRT within 1 week of life due to anuric ESRD from 2009-2019 at a single tertiary center. Primary outcomes were receipt of renal transplant (RT), one-year survival, and overall survival.RESULTS: Five patients met the inclusion criteria. Two patients received an RT. One-year survival was 80%, while overall survival was 60% with a median follow-up of 18 months. In the 2 still-living patients who have not undergone RT, they are ineligible, one due to recent malignancy and the other from acquired cardiovascular comorbidities.CONCLUSION: Patients with anuric ESRD requiring RRT undergo multiple treatment challenges with low RT and survival rates. These findings should be shared with families considering intervention for cases of severe renal disease diagnosed prenatally.

  View details for DOI 10.1038/s41372-022-01328-2

  View details for PubMedID 35121797

• Measurement of glomerular filtration rate reveals that subcapsular injection of shear-thinning hyaluronic acid hydrogels does not impair kidney function in mice. Journal of biomedical materials research. Part A Soranno, D. E., Kirkbride-Romeo, L., Han, D., Altmann, C., Rodell, C. B. 2021

  Abstract

  The continued development of minimally invasive therapeutic implants, such as injectable hydrogels, necessitates the concurrent advancement of methods to best assess their biocompatibility via functional outcomes in vivo. Biomaterial implants have been studied to treat kidney disease; however, assessment of biocompatibility has been limited to biomarker and histological assessments. Techniques now exist to measure kidney function serially in vivo in murine studies via transcutaneous measurements of glomerular filtration rate (tGFR). In this study, adult male and female wild-type BalbC mice underwent right unilateral nephrectomy. The remaining solitary left kidney was allowed 4weeks to recover via compensatory hypertrophy, after which subcapsular injection of either saline or shear-thinning hyaluronic acid hydrogel was performed. Serial tGFR measurements before and after treatment were used to assess the effect of hydrogel injection on kidney filtration. Urine and serum biomarkers of kidney function, and kidney histology were also quantified. Hydrogel injection did not affect kidney function, as assessed by tGFR. Results were in agreement with standard metrics of serum and urine biomarkers of injury as well as histological assessment of inflammation. The model developed provides a direct functional assessment of implant compatibility for the treatment of kidney disease and impact on kidney function.

  View details for DOI 10.1002/jbm.a.37317

  View details for PubMedID 34590787