Tissue fibrosis is associated with the aging process of most of our organs, and organ aging correlates with the chronic accumulation of senescent cells. Fibrosis occurs when fibroblasts proliferate and deposit pathological amounts of extracellular matrix (ECM), leading to progressive tissue scarring and organ dysfunction. Fibroblasts play a key role in fibrosis, especially in the skin where fibroblasts are the most abundant cell type in the dermis and are mainly responsible for the synthesis of ECM. This study aims to investigate how senescent fibroblasts and their secretome influence dermal fibrosis. Here we used human dermal fibroblasts (HDFs) treated with doxorubicin (doxo) to induce senescence. The senescent phenotype of these stress-induced premature senescent (SIPS) cells was confirmed with several markers. The expression of pro-fibrotic genes was quantified and finally, the impact of their secretome on the fibrotic response of non-senescent fibroblasts was assessed. Doxorubicin treatment, induced senescence in fibroblasts which has been confirmed with elevated senescence-associated β- galactosidase (SA-β-gal) activity, absence of BrdU incorporation, upregulation of p21, and loss of Lamin b1. Expression levels of the pro-fibrotic genes ACTA2 and FN1 increased in SIPS cells, but in contrast to studies using lung fibroblasts the secretome of these cells failed to induce a paracrine fibrotic response in non-senescent cells. In general, these results suggest that these senescent cells are potentially profibrotic, and their accumulation can trigger fibrosis in organs.

Introduction: Inflammation is one of the most important mechanisms involved in cisplatin-induced acute kidney injury (AKI). Mesenchymal stromal/stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory abilities. Human endometrial stromal/stem cells (hEnSCs) exhibit similar properties to MSCs. These cells secrete immunoregulators, so we investigated the inflammatory aspect of hEnSCs in the treatment of cisplatin-induced AKI in Wistar rats. Methods: Each group consisted of 6 male Wistar rats. Groups were as follows: sham, model (5 mg/kg cisplatin, IP), and treatment (1 million hEnSCs, IV, 3 hours after cisplatin). Renal function, histopathology, proliferation rate, infiltration of CD3+ T cell, and expression of Il-10 and cystatin c (Cst3) were assessed on day 5. DiI-labeled cells were tracked in kidney and liver on days 4 and 14. Results: HEnSC transplantation improved cisplatin-induced injuries such as renal dysfunction and tissue damage. The highest levels of pathologic scores and hyaline cast formation were observed in the model group while hEnSCs transplantation resulted in their reduction (154.00 ± 14.95, 8.00 ± 1.41 vs. 119.40 ± 5.43, 2.50 ± 1.05). The percentage of Ki-67 positive cells in the treatment group increased while cisplatin decreased proliferation (39.91 ± 5.33 vs. 23.91 ± 3.57 in glomeruli and 39.07 ± 2.95 vs. 16.61 ± 3.25 in tubules). The expression of Cst3 and Il-10 was higher in the model and treatment groups, respectively. DiI-labeled cells were observed in the renal tubules and liver lobes on days 4 and 14. Conclusion: HEnSCs may ameliorate cisplatin-induced AKI through anti-inflammatory and immunomodulatory effects and/or through paracrine effects.

Tissue fibrosis is associated with the aging process of most of our organs, and organ aging correlates with the chronic accumulation of senescent cells. Fibrosis occurs when fibroblasts proliferate and deposit pathological amounts of extracellular matrix (ECM), leading to progressive tissue scarring and organ dysfunction. Fibroblasts play a key role in fibrosis, especially in the skin where fibroblasts are the most abundant cell type in the dermis and are mainly responsible for the synthesis of ECM. This study aims to investigate how senescent fibroblasts and their secretome influence dermal fibrosis. Here we used human dermal fibroblasts (HDFs) treated with doxorubicin (doxo) to induce senescence. The senescent phenotype of these stress-induced premature senescent (SIPS) cells was confirmed with several markers. The expression of pro-fibrotic genes was quantified and finally, the impact of their secretome on the fibrotic response of non-senescent fibroblasts was assessed. Doxorubicin treatment, induced senescence in fibroblasts which has been confirmed with elevated senescence-associated β- galactosidase (SA-β-gal) activity, absence of BrdU incorporation, upregulation of p21, and loss of Lamin b1. Expression levels of the pro-fibrotic genes ACTA2 and FN1 increased in SIPS cells, but in contrast to studies using lung fibroblasts the secretome of these cells failed to induce a paracrine fibrotic response in non-senescent cells. In general, these results suggest that these senescent cells are potentially profibrotic, and their accumulation can trigger fibrosis in organs.

Oligodendrocytes are types of cells in central neural system (CNS). Their main function is generation of Myelin sheath in CNS, this sheath insulates the Axons. Any disorder in the function of these cells leads to demyelination of neurons and causes neural disorders including multiple sclerosis (MS). Nowadays, cell therapy provides plenty of hope for cure of MS. So far it has used different sources such as stem cells or progenitor for cell therapy of neural system. But each of them had some limitations, for instance using neural stem cells requires certain amount of CNS tissue. Embryonic stem cells also introduced as another candidate for cell therapy but due to some moral problems, such as necessity to creating a Blastocyst, using these cells accompanied many limitations. In cell therapy, the most important factor is facility to acquiring stem cells. iPS cells are kinds of Induced Pluripotent Stem cells which directly created by transferring of 4 transcription factors: oct4, sox2, klf2, and c-Myc into the differentiated cells. iPS cells are like pluripotent embryonic stem cells although they do not require demolition of Blastocyte. Endometrial Stromal cells are kinds of mesenchyme or adult cells which have been proven in human and mice’s uterine endometrial and they are easy to access. Both of these types of cells can be appropriate candidates for cell therapy. In this research we use these two types of cells for differentiate to Oligodendrocytes and we are able to differentiate iPS cells which are from human's eye and also human Endometrial Stromal cells to pre-Oligodendrocytes. Also we can compare their differentiation ability. These cells can be used for transplanting in MS patients.