Mesangial Damage and Repair: The Role of Stem Cells. A 6D Living Cell Model.
Jiamin Teng, Elba A Turbat-Herrera, Guillermo A Herrera. Nephrocor, Tempe, AZ
Background: In light chain deposition disease and AL-amyloidosis, mesangial cells are injured by GLCs resulting in MC apoptosis. However, the changes that occur in the mesangium are diametrically different. In AL-amyloidosis, mesangiolysis occurs whie in light chain deposition disease, the matrix increased and changes its compostion. Repair mechanisms of the affected mesangium are poorly understood. Stem cells may play an important role in repairing the damaged mesangium, especially since not many mesangial cells typically remain after the damage.
Design: Rat MCs were cultured on Matrigel loaded glass bottomed multi-well plates with 10% FBS/RPMI 1640 until confluence. MCs were then made quiescent by incubating them with 0.5% FBS/RPMI for 48 hours and then treated with LCDD and AL-AmLCs (10 ug/ml) purified from the urine of patients with renal biopsy proven conditions. Rat mesenchyma stem cells (RMSCs) are then stained with PKH-2 fluorescence or with Lysotracker Texas Red and placed 96 hours later into the wells of GLCs treated MCs for 2 weeks. The entire process is carefully monitored with sequential photos every 15 minutes using a 6D living cell model. This allows to observe the process of mesangial damage and how stem cells repair the damage.
Results: MCs treated with LCDD-LCs produced large amounts of matrix and formed nodules and those treated with AL-Am LCs engaged in the production of amyloid. MSCs cleaned up apoptotic MCs and eventually replaced injured cells becoming the majority of the cell mass. The amount of matrix material and amyloid decreased proportionally to the number of MSCs replacing the original MCs.
Conclusions: The reported observations with the 6D living cell imaging system demonstrated that the GLC-induced alterations are not irreversible and highlight a crucial role for MSCs replacing injured MCs and re-establishing mesangial homeostasis. In light chain deposition disease the process is complicated by the need to initially completely break down the abnormal accumulated matrix. These results suggest a therapeutic role for MSCs in repairing glomerular damage.
Category: Kidney (does not include tumors)
Monday, February 28, 2011 1:15 PM
Platform Session: Section H, Monday Afternoon