Follicular Development of Aged Rats Ovarian Injected Human Umbilical Cord Mesenchymal Stem Cells

Female reproductive system showing the fastest signs of aging. The ovarian aging characterized by a decrease in follicular development. Stem cells are undifferentiated cells and can form a variety of different cells as the foundation of tissues and organs. Previous studies reported that Bone Marrow Mesenchymal Stem Cells (BM-MSCs) transplantation can restore follicular development in damaged ovarian rats. This study aimed to analyze the number of follicular development in aged rats and to analyze the capability of human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) to improving follicular development in aged rats. This study used 3 mature rats (4 months old), and 9 nine aged rats (22-24 months old), Spraque Dawley (SD) strain. They were divided into four groups. The first and the second group was mature rats and aged rats without injection. The third and the fourth group was aged rats injected hUC-MSCs dose 106 cells/kgBW and hUC-MSCs dose 107 cells/kgBW. The injection carried out 4 times at 3-month intervals. The parameters observed were follicular development and homing image of hUC-MSCs in ovarian tissue. The results showed that the number of follicular developments in aged rats 22-24 months decreased significantly compared to mature rats 4 months old. Injection of hUC-MSCs at dose 106 cells/kgBW and 107 cells/kgBW did not increase follicular development in aged rats. hUC-MSCs did not found in ovarian tissue. It could be concluded that aged rats 22-24 months old no longer productive indicated from the number of follicular developments and corpus luteum decreased. The injection of hUC-MSCs intravenously did not indicate an improvement of follicular development in aged rats 22-24 months old

Penyuntikan Human Wharton’s Jelly Mesenchymal Stem Cells terhadap Perbaikan Fungsi Testis pada Tikus Tua Fisiologis (HUMAN WHARTON’S JELLY MESENCHYMAL STEM CELLS INJECTION AMELIORATE TESTICULAR FUNCTION ON PHYSIOLOGICAL AGING MALE RATS)

The most common therapy on men who suffered fertility decline due to aging was called “T Therapy”, but that’s therapy has long-term risks of sexual dysfunction, metabolic syndrome, prostate, and cardiovascular system. Stem cells are an alternative therapy can be used for ameliorate testicular fuction because of their ability to differentiate into various cell types. The aim of this study was to evaluate the injection of hWJ-MSC in physiologic aging male rats on testicular function. This study was used 3 young male rats (8-12 weeks) and 6 physiological aging male rats (22-24 months) which divided into 3 groups, (i) the young rats, (ii) physiological aging male rats, and (iii) physiological aging male rats that injected with hWJ-MSCs. The young rat group did not give any treatment, physiological aging male rats received NaCl (0.9%) 0.4 mL, and the treatment group received 1x106 cells/kg BW of hWJ-MSCs. The observations were performed on the macroscopical and histological analysis. The result indicates that the younger group had the lowest body weight (154.6 g) and the percentage of the testis weight on the body weight was highest (2.2%) compared to the other groups (P>0.05). The physiological aging rats group had the smallest tubule (9726.9 ìm2) with a largest interstitial area (1117.1 ìm2) compared the other groups (P>0.05). After injection of hWJ-MSC, the tubule area became wider followed by narrowing of the interstitial area (P>0.05). The difference in the body weights is due to the different age of the rat. Improvement of tubule area and interstitial area due to the ability of hWJ-MSCs to improve spermatogenic cells within the tubule. Injection of hWJ-MSCs has been shown to increase fertility in aging rats

Identification of novel players implicated in replication-dependent and independent DNA interstrand crosslink (ICL) repair

The integrity of the genome is constantly under threat from within and without. Cells rely on the evolutionary conserved DNA damage response (DDR) mechanism to orchestrate the repair of DNA lesions and thus prevent the accumulation of mutations. One of the most deleterious types of DNA lesions, interstrand crosslink (ICL), occurs when a crosslinking agent forms covalent bonds with both strands of the double helix and tethers them together. The most well-studied among ICL repair pathways is the Fanconi Anaemia (FA) pathway, the disruption of which gives rise to a disorder of the same name. Both the FA pathway and the more recently-discovered NEIL3 pathway are replication-dependent. However, replication-independent pathways also exist and they are likely responsible for the repair of ICLs in non-dividing cells. This thesis describes the optimisation of a purification scheme, which was designed to identify hitherto unknown players in ICL repair out of a pool of nuclear proteins. The scheme exploited the likely binding preference of such proteins for crosslinked over non-modified DNA probes. Two types of probes, linear and replication fork mimic, were designed to capture the proteins putatively associated with replication-independent and -dependent ICL repair pathways, respectively. The scheme was successfully used to identify UHRF1 and BOD1L1, two proteins with already known links to ICL repair, as well as THYN1, an EVE-domain-containing protein with no established roles in DDR. THYN1 is rapidly recruited to ICL sites in vivo and its absence confers hypersensitivity to psoralen-induced ICLs. THYN1 operates in the same pathway as FANCD2 in the repair of psoralen-derived lesions; however, unlike FANCD2, its activity is not cell cycle-dependent. Interestingly, THYN1 exerts a negative influence on MMC and cisplatin repair in FANCD2-deficient cells. Identification and analysis of putative THYN1 binding partners may help to explain this phenotype and to elucidate the molecular mechanisms which underpin THYN1-mediated repair

Spatial learning and memory of young and aging rats following injection with human Wharton’s jelly‐mesenchymal stem cells

Human Wharton’s jelly‐mesenchymal stem cells (hWJ‐MSC) are an emerging potential source of stem cells derived from the umbilical cord. Previous studies have shown their potential as treatment for traumatic brain injury and Parkinson’s disease. However, no study has yet investigated the effect of hWJ‐MSC injections in countering spatial learning and memory impairment in aging rats. The effect of hWJ‐MSC injection on young rats is also unknown. The objective of this research was to analyze the effect of an hWJ‐MSC injection on spatial learning, memory, density of putative neural progenitor cells (pNPC), and neuronal apoptosis in the dentate gyrus (DG) of young and aging rats. Injection of hWJ‐MSC did not change spatial learning and memory in young rats until two months post‐injection. This might be due to retained pNPC density and neuronal apoptosis in the DG of young rats after injection of hWJ‐MSC. In contrast, injection of hWJ‐MSC promoted both spatial learning and memory in aging rats, a finding that might be attributable to the increased pNPC density and attenuated neuronal apoptosis in DG of aging rats during the two months post‐injection. Our study suggests that a single injection of hWJ‐MSC might be sufficient to promote improvement in long‐term learning and memory in aging rats