A novel in vitro retinal differentiation model by co-culturing adult human bone marrow stem cells with retinal pigmented epithelium cells

Abstract Human bone marrow stem cells (BMSCs) are heterogeneous progenitor cells with two defining features, self-renew and multi-lineage differentiation. As one of the differentiation directions, osteogenesis is vital for bone homeostasis. A growing body of evidences show that ubiquitin-dependent protein degradation plays an essential role in the osteogenic differentiation of BMSCs. In this study, we found that LMCD1 was upregulated during osteogenic differentiation process of BMSCs by analyzing GSE80614. In vitro and in vivo functional studies confirmed that LMCD1 was critical to the osteogenic commitment of BMSCs. Compared to those of the controls, downregulation of LMCD1 significantly restrained osteogenic differentiation and enhanced adipogenic differentiation, while upregulation of LMCD1 increased the osteogenic differentiation and suppressed adipogenic differentiation. Mechanically, we found that LMCD1 could protect RUNX2 and Smad1 protein from Smurf1-induced ubiquitination degradation thereby regulating BMP signaling. In conclusion, our findings suggest that LMCD1 is a novel regulator of osteogenic differentiation and may be a potential therapeutic target for bone metabolism related diseases.

Download Full-text

Neuro-glial differentiation of human bone marrow stem cells in vitro

Experimental Neurology ◽

10.1016/j.expneurol.2004.12.013 ◽

2005 ◽

Vol 193 (2) ◽

pp. 312-325 ◽

Cited By ~ 143

Author(s):

P. Bossolasco ◽

L. Cova ◽

C. Calzarossa ◽

S.G. Rimoldi ◽

C. Borsotti ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Bone Marrow Stem Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Glial Differentiation

Download Full-text

Biphasic Dose–Response and Hormetic Effects of Stress Hormone Hydrocortisone on Telomerase-Immortalized Human Bone Marrow Stem Cells In Vitro

Dose-Response ◽

10.1177/1559325819889819 ◽

2019 ◽

Vol 17 (4) ◽

pp. 155932581988981 ◽

Cited By ~ 3

Author(s):

Indra Kumar Gopi ◽

Suresh I. S. Rattan

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Dose Response ◽

Stress Hormones ◽

Bone Marrow Stem Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Mild Stress ◽

Wide Range

Although high levels of stress hormones are associated with well-known negative health outcomes, their low levels can have health-promoting effects by virtue of the phenomenon of mild stress-induced hormesis. We have studied the effects of a wide range (between 100 nmol/L and 150 μmol/L) of hydrocortisone (HC) on human bone marrow stem cells in vitro. Telomerase-immortalized human mesenchymal stem cells (hTERT-MSCs) were exposed to various doses of HC for different durations (1-6 days) and analyzed for survival and metabolic activity by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, for cell migratory ability by a wound-healing assay and for osteoblastic and adipogenic differentiation abilities in vitro. Our findings indicate that hTERT-MSCs exposed to HC resulted in a biphasic hormetic dose–response in some measures but not all. Although the mitochondrial and metabolic MTT activity assay clearly showed low-level stimulatory (between 0.1 and 1 µmol/L) and high-level inhibitory effects (from about 10 µmol/L onward), the cytostatic and differentiation-inducing effects were mostly linear at concentrations between 1 and 100 µmol/L. Further long-term studies will elucidate whether chronic or intermittent exposure of human cells to stress hormones has physiologically beneficial hormetic effects.

Download Full-text