Stem Cells and Cloning-Advances and Applications最新文献

The intervertebral disc (IVD) is an important structure in the human body because it functions as a weight-bearing. This structure undergoes a process of degeneration like the rest of the body and this process is known as intervertebral disc degeneration (IDD) which is the most common cause of low back pain (LBP). The current common management, either conservative or surgical, is pain-relieving and has not been able to restore degenerated disc optimally. Changes in the IVD microenvironment in IDD conditions make it difficult for the regeneration process to occur. Research to reverse the degeneration process continues to develop, one of them is the use of adipose-derived stem cells (ASCs). ASCs is superior due to the ability to differentiate into several other cells such as adipocytes, chondrocytes, and osteoblasts, it also has ability to act as immunomodulators by stimulating the migration of immune cells to damaged tissues. ASCs becomes a good choice because it is easy to obtain, low donor site morbidity, high proliferation rate, and excellent differentiation abilities. Research on the optimal preparation process for ASCs and their application to various disorders continues to advanced. This study aims to review the potential use of ASCs for regeneration of intervertebral disc degeneration.

Traumatic brain injury is the main cause of injury-related deaths and disabilities throughout the world, which is characterized by a disruption of the normal physiology of the brain following trauma. It can potentially cause severe complications such as physical, cognitive, and emotional impairment. In addition to understanding traumatic brain injury pathophysiology, this review explains the therapeutic potential of stem cells following brain injury in two pathways: response of endogenous neurogenic cells and transplantation of exogenous stem cell therapy. After traumatic brain injuries, clinical evidence indicated that endogenous neural progenitor cells might play an important role in regenerative medicine to treat brain injury. This is due to an increased neurogenic regeneration ability of these cells following brain injury. Besides, exogenous stem cell transplantation has also accelerated immature neuronal development and increased endogenous cellular proliferation in the damaged brain region. Therefore, a better understanding of the endogenous neural stem cell's regenerative ability and the effect of exogenous stem cells on proliferation and differentiation ability may help researchers to understand how to increase functional recovery and tissue repair following injury.

Introduction: High-efficacy single-cell cloning of human-induced pluripotent cells (IPSCs) remains a major challenge. The development of a culture method that supports single-cell passaging while maintaining reproducibility, homogeneity, scalability, and cell expansion to clinically relevant numbers is necessary for clinical application.

Methods: To address this issue, we combined the use of the rho-associated protein kinase (ROCK) inhibitor Y-27632 and hypoxic conditions in culture to produce a novel, efficient single-cell culture method for human IPSCs and embryonic stem cells.

Results: Through immunocytochemistry, alkaline phosphatase assays, and flow cytometry, we demonstrated that our method enabled high single-cell proliferation while maintaining self-renewal and pluripotency abilities.

Discussion: We showed the beneficial effect of the interaction between hypoxia and ROCK inhibition in regulating cell proliferation, pluripotency, and single-cell survival of pluripotent cells.

Background: Umbilical cord mesenchymal stem cells (UC-MSCs)-derived secretome is currently used in regenerative therapy. MSCs are believed to secrete a wide spectrum of bioactive molecules which give paracrine effects in immunomodulation and regenerative capacities. One group that was found in secretome is interleukins (ILs), a cytokine that plays an essential role in the process of proliferation, differentiation, maturation, migration, and adhesion of immune cells. However, as there are many types of ILs, the profile of ILs in the UC-MSCs-derived secretome has been limitedly reported. Therefore, in this study, we would like to profile and detect the interleukin concentration secreted by UC-MSCs.

Methods: UC-MSCs-derived secretome was collected from UC-MSCs passage 5 after 24- and 48-hour incubation (n=9). Secretome was filtered using 0.2 µm and stored at -80°C for further detection. All samples were normalized before the interleukin (IL-2, IL-4, IL-6, IL-9, IL-10, IL-12, IL-17A) detection using a MACSPlex Cytokine Kit.

Results: The IL-6 has the highest concentration among other interleukins in both groups and increases significantly (p<0.003) after incubation for 48 hours. The pro-inflammatory factors are decreasing while anti-inflammatory factors are increasing after 48-hour incubation.

Discussion: Our studies show that the UC-MSCs secrete pro- and anti-inflammatory interleukins. The concentration of anti-inflammatory interleukins shows to be increasing, while the pro-inflammatory interleukins are decreasing within the longer incubation time, but this not be applicable for IL-10 and IL-6. IL-6 has the highest concentration among other ILs. These results may provide important clues regarding when is the right time for secretome to be used in therapy patients, because all the molecules in the secretome can lead to many clinical manifestations.

Introduction: Mesenchymal stem cells (MSCs) have been postulated by a number of authors to be the precursor cells of fibroblasts and myofibroblasts in keloids. They have been seen as a regenerative pool that ensures a steady supply of cells. The objective of our study was to determine MSCs in keloids and normal skin as a determinant of keloid recurrence.

Methods: This was a longitudinal prospective study in which patients with keloid excisions of their specimens analyzed for MSC. A control group of patients matched for age, sex, and body-mass index (BMI) with no history of keloids admitted for elective surgical procedures had their skin samples taken and also analyzed for MSCs. Data collected were analyzed and compared using Student's t, x ², and Fisher's exact t tests.

Results: A total of 61 patients with keloids and a control group of 32 patients were recruited. The male:female ratio was 1:2 and mean age 29.5 and 29.7 years for keloids and controls, respectively. Patients with recurrent keloids had a mean density of 841.4 MSCs/g compared to 578 MSCs/g of tissue for those with no recurrence and 580 MSCs/g for patients with normal skin. Recurrent keloids had a significantly higher percentage of MSCs than those without.

Conclusion: Keloids compared to normal skin had a higher percentage of MSCs, with recurrent keloids demonstrating an even higher count, a possible indicator that MSCs might correlate with severity of keloid disease and recurrence.

Introduction: Stroke is a leading cause of death and disability worldwide. The disease is caused by reduced blood flow into the brain resulting in the sudden death of neurons. Limited spontaneous recovery might occur after stroke or brain injury, stem cell-based therapies have been used to promote these processes as there are no drugs currently on the market to promote brain recovery or neurogenesis. Adult stem cells (ASCs) have shown the ability of differentiation and regeneration and are well studied in literature. ASCs have also demonstrated safety in clinical application and, therefore, are currently being investigated as a promising alternative intervention for the treatment of stroke.

Methods: Eleven studies have been systematically selected and reviewed to determine if autologous adult stem cells are effective in the treatment of stroke. Collectively, 368 patients were enrolled across the 11 trials, out of which 195 received stem cell transplantation and 173 served as control. Using data collected from the clinical outcomes, a broad comparison and a meta-analysis were conducted by comparing studies that followed a similar study design.

Results: Improvement in patients' clinical outcomes was observed. However, the overall results showed no clinical significance in patients transplanted with stem cells than the control population.

Conclusion: Most of the trials were early phase studies that focused on safety rather than efficacy. Stem cells have demonstrated breakthrough results in the field of regenerative medicine. Therefore, study design could be improved in the future by enrolling a larger patient population and focusing more on localized delivery rather than intravenous transplantation. Trials should also introduce a more standardized method of analyzing and reporting clinical outcomes to achieve a better comparable outcome and possibly recognize the full potential that these cells have to offer.