Extracorporeal Stromal Cell Therapy for Subjects With Dialysis-Dependent Acute Kidney Injury

Brian L.K. Miller, Payal Garg, Ben Bronstein, Elizabeth LaPointe, Herb Lin, David M. Charytan, Arno W. Tilles, Biju Parekkadan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: The pathophysiology of acute kidney injury (AKI) involves damage to renal epithelial cells, podocytes, and vascular beds that manifests into a deranged, self-perpetuating immune response and peripheral organ dysfunction. Such an injury pattern requires a multifaceted therapeutic to alter the wound healing response systemically. Mesenchymal stromal cells (MSCs) are a unique source of secreted factors that can modulate an inflammatory response to acute organ injury and enhance the repair of injured tissue at the parenchymal and endothelial levels. This phase Ib/IIa clinical trial evaluates SBI-101, a combination product that administers MSCs extracorporeally to overcome pharmacokinetic barriers of MSC transplantation. SBI-101 contains allogeneic human MSCs inoculated into a hollow-fiber hemofilter for the treatment of patients with severe AKI who are receiving continuous renal replacement therapy (CRRT). SBI-101 therapy is designed to reprogram the molecular and cellular components of blood in patients with severe organ injury. Methods: This study is a prospective, multicenter, randomized, double-blind, sham-controlled, study of subjects with a clinical diagnosis of AKI who are receiving CRRT. Up to 32 subjects may be enrolled to provide 24 evaluable subjects (as a per protocol population). Subjects will receive CRRT in tandem with a sham control (0 MSCs), or the low- (250 × 10 6 MSCs) or high-dose (750 × 10 6 MSCs) SBI-101 therapeutic. Results: The study will measure dose-dependent safety, renal efficacy, and exploratory biomarkers to characterize the pharmacokinetics and pharmacodynamics of SBI-101 in treated subjects. Conclusion: This first-in-human clinical trial will evaluate the safety and tolerability of SBI-101 in patients with AKI who require CRRT.

Original languageEnglish (US)
Pages (from-to)1119-1127
Number of pages9
JournalKidney International Reports
Volume3
Issue number5
DOIs
StatePublished - Sep 1 2018

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Stromal Cells
Cell- and Tissue-Based Therapy
Mesenchymal Stromal Cells
Acute Kidney Injury
Dialysis
Renal Replacement Therapy
Wounds and Injuries
Pharmacokinetics
Clinical Trials
Kidney
Safety
Podocytes
Cell Transplantation
Therapeutics
Wound Healing
Blood Vessels
Biomarkers
Epithelial Cells
Population

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Miller, Brian L.K. ; Garg, Payal ; Bronstein, Ben ; LaPointe, Elizabeth ; Lin, Herb ; Charytan, David M. ; Tilles, Arno W. ; Parekkadan, Biju. / Extracorporeal Stromal Cell Therapy for Subjects With Dialysis-Dependent Acute Kidney Injury. In: Kidney International Reports. 2018 ; Vol. 3, No. 5. pp. 1119-1127.
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abstract = "Introduction: The pathophysiology of acute kidney injury (AKI) involves damage to renal epithelial cells, podocytes, and vascular beds that manifests into a deranged, self-perpetuating immune response and peripheral organ dysfunction. Such an injury pattern requires a multifaceted therapeutic to alter the wound healing response systemically. Mesenchymal stromal cells (MSCs) are a unique source of secreted factors that can modulate an inflammatory response to acute organ injury and enhance the repair of injured tissue at the parenchymal and endothelial levels. This phase Ib/IIa clinical trial evaluates SBI-101, a combination product that administers MSCs extracorporeally to overcome pharmacokinetic barriers of MSC transplantation. SBI-101 contains allogeneic human MSCs inoculated into a hollow-fiber hemofilter for the treatment of patients with severe AKI who are receiving continuous renal replacement therapy (CRRT). SBI-101 therapy is designed to reprogram the molecular and cellular components of blood in patients with severe organ injury. Methods: This study is a prospective, multicenter, randomized, double-blind, sham-controlled, study of subjects with a clinical diagnosis of AKI who are receiving CRRT. Up to 32 subjects may be enrolled to provide 24 evaluable subjects (as a per protocol population). Subjects will receive CRRT in tandem with a sham control (0 MSCs), or the low- (250 × 10 6 MSCs) or high-dose (750 × 10 6 MSCs) SBI-101 therapeutic. Results: The study will measure dose-dependent safety, renal efficacy, and exploratory biomarkers to characterize the pharmacokinetics and pharmacodynamics of SBI-101 in treated subjects. Conclusion: This first-in-human clinical trial will evaluate the safety and tolerability of SBI-101 in patients with AKI who require CRRT.",
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Miller, BLK, Garg, P, Bronstein, B, LaPointe, E, Lin, H, Charytan, DM, Tilles, AW & Parekkadan, B 2018, 'Extracorporeal Stromal Cell Therapy for Subjects With Dialysis-Dependent Acute Kidney Injury', Kidney International Reports, vol. 3, no. 5, pp. 1119-1127. https://doi.org/10.1016/j.ekir.2018.05.009

Extracorporeal Stromal Cell Therapy for Subjects With Dialysis-Dependent Acute Kidney Injury. / Miller, Brian L.K.; Garg, Payal; Bronstein, Ben; LaPointe, Elizabeth; Lin, Herb; Charytan, David M.; Tilles, Arno W.; Parekkadan, Biju.

In: Kidney International Reports, Vol. 3, No. 5, 01.09.2018, p. 1119-1127.

Research output: Contribution to journalArticle

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T1 - Extracorporeal Stromal Cell Therapy for Subjects With Dialysis-Dependent Acute Kidney Injury

AU - Miller, Brian L.K.

AU - Garg, Payal

AU - Bronstein, Ben

AU - LaPointe, Elizabeth

AU - Lin, Herb

AU - Charytan, David M.

AU - Tilles, Arno W.

AU - Parekkadan, Biju

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Y1 - 2018/9/1

N2 - Introduction: The pathophysiology of acute kidney injury (AKI) involves damage to renal epithelial cells, podocytes, and vascular beds that manifests into a deranged, self-perpetuating immune response and peripheral organ dysfunction. Such an injury pattern requires a multifaceted therapeutic to alter the wound healing response systemically. Mesenchymal stromal cells (MSCs) are a unique source of secreted factors that can modulate an inflammatory response to acute organ injury and enhance the repair of injured tissue at the parenchymal and endothelial levels. This phase Ib/IIa clinical trial evaluates SBI-101, a combination product that administers MSCs extracorporeally to overcome pharmacokinetic barriers of MSC transplantation. SBI-101 contains allogeneic human MSCs inoculated into a hollow-fiber hemofilter for the treatment of patients with severe AKI who are receiving continuous renal replacement therapy (CRRT). SBI-101 therapy is designed to reprogram the molecular and cellular components of blood in patients with severe organ injury. Methods: This study is a prospective, multicenter, randomized, double-blind, sham-controlled, study of subjects with a clinical diagnosis of AKI who are receiving CRRT. Up to 32 subjects may be enrolled to provide 24 evaluable subjects (as a per protocol population). Subjects will receive CRRT in tandem with a sham control (0 MSCs), or the low- (250 × 10 6 MSCs) or high-dose (750 × 10 6 MSCs) SBI-101 therapeutic. Results: The study will measure dose-dependent safety, renal efficacy, and exploratory biomarkers to characterize the pharmacokinetics and pharmacodynamics of SBI-101 in treated subjects. Conclusion: This first-in-human clinical trial will evaluate the safety and tolerability of SBI-101 in patients with AKI who require CRRT.

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