Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes

Abstract

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca ) concentration. High Ca environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602.

Superoxide Dismutase 3-Transduced Mesenchymal Stem Cells Preserve Epithelial Tight Junction Barrier in Murine Colitis and Attenuate Inflammatory Damage in Epithelial Organoids

“…Briefly, human MSCs from umbilical cord blood were provided from Kangstem Biotech (Seoul, Korea). MSCs were prepared according to previously described methods [ 52 ], cultured in KSB-3 culture medium (Kangstem Biotech), and supplemented with 10% FBS (fetal bovine serum, GenDEPOT, Hanam, Korea) and 1% penicillin-streptomycin (LS202–02, Welgene, Gyeongsan-si, Korea) at 37 °C, 5% CO 2 . Lenti-M1.9-SOD3 was provided by Chungnam National University and used to infect MSCs.…”

Mesenchymal Stem Cells Regenerate Diabetic Foot Ulcers: A Review Article

“…In addition, the beneficial effects of MSCs-conditioned media on the keratinocytes, paracrine signaling activity, proliferation, and migration of keratinocytes have been demonstrated 56 . TGFβ1 shows MSCs paracrine signaling via decreasing suppression of differentiation, thus leading to increase proliferation of keratinocytes 57 , 58 ( Table 2 ). Generally, MSCs transplantation stimulates proliferation and migration of the predominant cell types in the wound by release soluble factors 59 ( Figure.1 ).…”