Prevention of Transition from Acute Kidney Injury to Chronic Kidney Disease Using Clinical-Grade Perinatal Stem Cells in Non-Clinical Study.
Agne GrygucJustinas MaciulaitisLukas MickeviciusArvydas LaurinaviciusNeringa SutkevičienėRamune GrigaleviciuteVilma ZigmantaiteRomaldas MaciulaitisInga Arune BumblytePublished in: International journal of molecular sciences (2024)
Acute kidney injury (AKI) is widely recognized as a precursor to the onset or rapid progression of chronic kidney disease (CKD). However, there is currently no effective treatment available for AKI, underscoring the urgent need for the development of new strategies to improve kidney function. Human placental mesenchymal stromal cells (hpMSCs) were isolated from donor placentas, cultured, and characterized with regard to yield, viability, flow cytometry, and potency. To mimic AKI and its progression to CKD in a rat model, a dedicated sensitive non-clinical bilateral kidney ischemia-reperfusion injury (IRI) model was utilized. The experimental group received 3 × 10 5 hpMSCs into each kidney, while the control group received IRI and saline and the untreated group received IRI only. Urine, serum, and kidney tissue samples were collected over a period of 28 days. The hpMSCs exhibited consistent yields, viability, and expression of mesenchymal lineage markers, and were also shown to suppress T cell proliferation in a dose-dependent manner. To ensure optimal donor selection, manufacturing optimization, and rigorous quality control, the rigorous Good Manufacturing Practice (GMP) conditions were utilized. The results indicated that hpMSCs increased rat survival rates and improved kidney function by decreasing serum creatinine, urea, potassium, and fractionated potassium levels. Furthermore, the study demonstrated that hpMSCs can prevent the initial stages of kidney structural fibrosis and improve kidney function in the early stages by mitigating late interstitial fibrosis and tubular atrophy. Additionally, a robust manufacturing process with consistent technical parameters was established.
Keyphrases
- acute kidney injury
- chronic kidney disease
- end stage renal disease
- cardiac surgery
- stem cells
- flow cytometry
- quality control
- cell proliferation
- endothelial cells
- ischemia reperfusion injury
- bone marrow
- oxidative stress
- poor prognosis
- healthcare
- small cell lung cancer
- escherichia coli
- long non coding rna
- cystic fibrosis
- biofilm formation
- mesenchymal stem cells
- high glucose
- cell cycle
- staphylococcus aureus
- metabolic syndrome
- quantum dots
- brain metastases
- replacement therapy