Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model

Moghadasali, Reza; Azarnia, Mahnaz; Hajinasrollah, Mostafa; H, Arghani; Nassiri, Seyed Mahdi; Molazem, Mohammad; Dizaj, Ahmad Vosough; Mohitmafi, Soroush; Najarasl, Mostafa; Ajdari, Zahra; Yazdi, Reza Salman; Bagheri, Mohsen; Ghanaati, Hossein; Rafiei, Behrouz; Gheisari, Yousof; Baharvand, Hossein; Aghdami, Nasser

doi:10.1016/j.jcyt.2014.01.004

Cited by 46 publications

(40 citation statements)

References 66 publications

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“…Some studies suggest that MSCs can act from distant organ sites (e.g., lung or spleen) to modulate inflammation and promote regeneration in the kidney . However, numerous other studies have shown that MSCs residing in the kidney tissue following infusion through the renal artery are capable of improving AKI . Because of the promising preclinical data, MSCs are being tested in clinical trials designed to prevent the occurrence of AKI (NCT01602328, NCT00733876; http://www.clinicaltrials.gov).…”

Section: Introductionmentioning

confidence: 99%

Pulsed Focused Ultrasound Pretreatment Improves Mesenchymal Stromal Cell Efficacy in Preventing and Rescuing Established Acute Kidney Injury in Mice

et al. 2015

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Animal studies have shown that mesenchymal stem cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24hr after cisplatin administration. These findings have spurred several human clinical trials to prevent AKI. However, no specific therapy effectively treats clinically obvious AKI or rescues renal function once advanced injury is established. We investigated if noninvasive image-guided pulsed focused ultrasound (pFUS) could alter the kidney microenvironment to enhance homing of subsequently infused MSC. To examine the efficacy of pFUS-enhanced cell homing in disease, we targeted pFUS to kidneys to enhance MSC homing after cisplatin-induced AKI. We found that pFUS enhanced MSC homing at 1 day post-cisplatin, prior to renal functional deficits, and that enhanced homing improved outcomes of renal function, tubular cell death, and regeneration at 5 days post-cisplatin compared to MSC alone. We then investigated whether pFUS+MSC therapy could rescue established AKI. MSC alone at 3 days post-cisplatin, after renal functional deficits were obvious, significantly improved 7-day survival of animals. Survival was further improved using pFUS+MSC. MSC, alone or with pFUS, changed kidney macrophage phenotypes from M1 to M2. This study shows pFUS is a neoadjuvant approach to improve MSC homing to diseased organs. pFUS with MSC better prevents AKI than MSC alone and allows rescue therapy in established AKI, which currently has no meaningful therapeutic options.

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Section: Introductionmentioning

confidence: 99%

Pulsed Focused Ultrasound Pretreatment Improves Mesenchymal Stromal Cell Efficacy in Preventing and Rescuing Established Acute Kidney Injury in Mice

et al. 2015

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“…Previously we showed the promising efficacy of transplanted MSCs in experimental models of chronic kidney disease (CKD) and acute kidney injury (AKI) [14–16]. We had indicated that MSC-derived conditioned medium induced renal tubular cell regeneration after nephrotoxicity induction [14], then we showed the bone marrow MSC (BMMSC) lowered serum creatinine (SCr) and urea levels and accelerated regulatory T cells (Tregs) in a monkey AKI model [15]. In a recent study, our results indicated that MSCs resulted in decreased CKD progression in a monkey model [16].…”

Section: Introductionmentioning

confidence: 99%

Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients

et al. 2017

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BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy disease characterized by progressive formation and enlargement of cysts in multiple organs. The kidneys are particularly affected and patients may eventually develop end-stage renal disease (ESRD). We hypothesize that bone marrow mesenchymal stromal cells (BMMSCs) are renotropic and may improve kidney function via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. In this study, we aim to assess the safety and tolerability of a BMMSC infusion in ADPKD patients.MethodsWe performed a single-arm phase I clinical trial with a 12-month follow-up. This study enrolled six eligible ADPKD patients with an estimated glomerular filtration rate (eGFR) of 25–60 ml/min/1.73 m2. Patients received autologous cultured BMMSCs (2 × 106 cells/kg) through the cubital vein according to our infusion protocol. We investigated safety issues and kidney function during the follow-up visits, and compared the findings to baseline and 1 year prior to the intervention.ResultsThere were no patients lost to follow-up. We observed no cell-related adverse events (AE) and serious adverse events (SAE) after 12 months of follow-up. The mean eGFR value of 33.8 ± 5.3 ml/min/1.73 m2 1 year before cell infusion declined to 26.7 ± 3.1 ml/min/1.73 m2 at baseline (P = 0.03) and 25.8 ± 6.2 ml/min/1.73 m2 at the 12-month follow-up visit (P = 0.62). The mean serum creatinine (SCr) level of 2 ± 0.3 mg/dl 1 year before the infusion increased to 2.5 ± 0.4 mg/dl at baseline (P = 0.04) and 2.5 ± 0.6 mg/dl at the 12-month follow-up (P = 0.96). This indicated significant changes between the differences of these two periods (12 months before infusion to baseline, and 12 months after infusion to baseline) in SCr (P = 0.05), but not eGFR (P = 0.09).ConclusionsThis trial demonstrated the safety and tolerability of an intravenous transplantation of autologous BMMSCs. BMMSC efficacy in ADPKD patients should be investigated in a randomized placebo-controlled trial with a larger population, which we intend to perform.Trial registrationClinicalTrials.gov, NCT02166489. Registered on June 14, 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0557-7) contains supplementary material, which is available to authorized users.

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“…We showed that MSC‐derived conditioned medium induces regeneration of renal tubular cell after nephrotoxicity induction (Moghadasali et al, ); also, we approved the BM‐MSCs lowered serum creatinine and urea levels and increased regulatory T cells in a monkey AKI model (Moghadasali et al, ). In a recent study, our results indicated that MSCs suppress CKD progression in a monkey model (Moghadasali et al, ).…”

Section: Cell Therapy In Adpkdmentioning

confidence: 90%

Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions

Malekshahabi

Rad

Serra

et al. 2019

Journal Cellular Physiology

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Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic inherited renal cystic disease that occurs in different races worldwide. It is characterized by the development of a multitude of renal cysts, which leads to massive enlargement of the kidney and often to renal failure in adulthood. ADPKD is caused by a mutation in PKD1 or PKD2 genes encoding the proteins polycystin‐1 and polycystin‐2, respectively. Recent studies showed that cyst formation and growth result from deregulation of multiple cellular pathways like proliferation, apoptosis, metabolic processes, cell polarity, and immune defense. In ADPKD, intracellular cyclic adenosine monophosphate (cAMP) promotes cyst enlargement by stimulating cell proliferation and transepithelial fluid secretion. Several interventions affecting many of these defective signaling pathways have been effective in animal models and some are currently being tested in clinical trials. Moreover, the stem cell therapy can improve nephropathies and according to studies were done in this field, can be considered as a hopeful therapeutic approach in future for PKD. This study provides an in‐depth review of the relevant molecular pathways associated with the pathogenesis of ADPKD and their implications in development of potential therapeutic strategies.

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Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model

Cited by 46 publications

References 66 publications

Pulsed Focused Ultrasound Pretreatment Improves Mesenchymal Stromal Cell Efficacy in Preventing and Rescuing Established Acute Kidney Injury in Mice

Pulsed Focused Ultrasound Pretreatment Improves Mesenchymal Stromal Cell Efficacy in Preventing and Rescuing Established Acute Kidney Injury in Mice

Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients

Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions

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