Innovations in CKRT: individualized therapy with fewer complications

Szamosfalvi, Balázs; Yessayan, Lenar

doi:10.1038/s41581-020-0326-1

Cited by 3 publications

(4 citation statements)

References 10 publications

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“…Furthermore, patients which are medically restricted from systemic heparin administration for risk of internal bleeding could potentially be anticoagulated regionally with citrate. Citrate could be introduced and equilibrated within the MSC bioreactor circuit, allowing MSC factors to be released but without exposing patients to the anticoagulant 67 …”

Section: Discussionmentioning

confidence: 99%

“…Citrate could be introduced and equilibrated within the MSC bioreactor circuit, allowing MSC factors to be released but without exposing patients to the anticoagulant. 67 In the unfortunate circumstances of the COVID-19 pandemic, interest in MSC based therapies has increased markedly. Case reports, first from China and then worldwide, showed promising improvements in patient health following intravenous MSC infusion, even in severely ill patients.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application

O’Rourke

Nguyen

Tilles

et al. 2021

Stem Cells Translational Medicine

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While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. In this system, MSCs are seeded on the exterior of a hollow-fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore-size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against directly injected "free" MSCs, a model of systemic administration. Our results showed that restricting MSCs exposure to plasma via a bioreactor extends the time necessary for clot formation to occur when compared with "free" MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Furthermore, application of this technology in two in vivo models did not require additional heparin in fully anticoagulated experimental animals to maintain target activated clotting time levels relative to heparin anticoagulated controls. Taken together the clinical use of bioreactor housed MSCs could offer a novel method to control systemic MSC exposure and prolong clot formation time.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application

O’Rourke

Nguyen

Tilles

et al. 2021

Stem Cells Translational Medicine

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“…Due to limited resources, blood collection immediately pre-and posttreatment to estimate urea reduction ratio was not pursued. Finally, similar to some other CRRT systems in the market, the current version of the SAMI does not yet have cloud-based services and integrated citrate and calcium pumps [20,21].…”

Section: Discussionmentioning

confidence: 99%

Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results

et al. 2020

Self Cite

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Introduction: The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. Material and Methods: Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. Results: On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had COVID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 – 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 – 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. Conclusion: Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.

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“…Further, patients which are medically restricted from systemic heparin administration for risk of internal bleeding could potentially be anticoagulated regionally with citrate. Citrate could be introduced and equilibrated within the MSC bioreactor circuit, allowing MSC factors to be released but without exposing patients to the anticoagulant [54].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cell Delivery via an Ex Vivo Bioreactor Preclinical Test System Attenuates Clot Formation for Intravascular Application

O’Rourke

Nguyen

Tilles

et al. 2020

Preprint

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While mesenchymal stromal cells (MSCs) are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novel ex vivo approach aimed at improving the safety of MSC systemic administration by use of a bioreactor. In this device, MSCs are seeded on the outside of a hollow-fiber filter, sequestering them behind a hemocompatible membrane, while still maintaining cross talk with blood cells and circulating signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against “free” MSCs, as a model of systemic administration, which were directly injected into the circuit. Our results showed that physical isolation of the MSCs via a bioreactor extends the time necessary for clot formation to occur when compared to “free” MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Further, application of this technology in two in vivo models did not require additional heparin to maintain target ACT levels relative to the acellular device. Taken together, the use of hollow fiber filters to house MSCs, if adopted clinically, could offer a novel method to control systemic MSC exposure and prolong clot formation time.

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Innovations in CKRT: individualized therapy with fewer complications

Cited by 3 publications

References 10 publications

Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application

Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application

Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results

Mesenchymal Stromal Cell Delivery via an Ex Vivo Bioreactor Preclinical Test System Attenuates Clot Formation for Intravascular Application

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