Paracrine factors for neurodegenerative disorders:special emphasis on Parkinson's disease

The progressive loss of dopaminergic neurons in the ventral mesencephalon is the main pathological hallmark of Parkinson’s disease（PD）.Drugs currently available only alleviate the principal symptomatic motor-related disturbances and their benefit is counteracted by side effects in the long time.

Adult stem cells as a tool for kidney regeneration

Kidney regeneration is a challenging but promisingstrategy aimed at reducing the progression to end-stagerenal disease （ESRD） and improving the quality of life of patients with ESRD. Adult stem cells are multipotent stem cells that reside in various tissues, such as bone marrow and adipose tissue. Although intensive studies to isolate kidney stem/progenitor cells from the adult kidney have been performed, it remains controversial whether stem/progenitor cells actually exist in the mammalian adult kidney. The effcacy of mesenchymal stem cells （MSCs） in the recovery of kidney function has been demonstrated in animal nephropathy models, such as acute tubular injury, glomerulonephritis, renal artery stenosis, and remnant kidney. However, their benefcial effects seem to be mediated largely via their paracrine effects rather than their direct differentiation into renal parenchymal cells. MSCs not only secrete bioactive molecules directly into the circulation, but they also release various molecules, such as proteins, mRNA, and microRNA, in membrane-covered vesicles. A detailed analysis of these molecules and an exploration of the optimal combination of these molecules will enable the treatment of patients with kidney disease without using stem cells. Another option for the treatment of patients with kidney disease using adult somatic cells is a direct/indirect reprogramming of adult somatic cells into kidney stem/progenitor cells. Although many hurdles still need to be overcome, this strategy will enable bona fde kidney regeneration rather than kidney repair using remnant renal parenchymal cells.

Stem Cell Therapy of Ischemic Heart Disease

Ischemic heart disease (IHD) accelerates death of cardiomyocytes and leads to the onset of cardiac failure. Due to the application of stem cells, there exists a potential for the regeneration of a damaged myocardium. Here we present a brief review of the modern data on the application of various types of stem cells for the IHD therapy. We consider different types of stem cells, which are most preferable for the clinical application, including mesenchymal stem cells, cardiac stem cells, embryonic stem cells, iPS cells and others. In particular, we discuss their advantages and strategies which can be applied in order to boost their regenerative potential, as well as optimization of their delivery. Besides, our review refers to the contemporary achievements in the field of tissue engineering of heart, using both polymer scaffolds and scaffold-free constructs. We also discuss the most prominent known clinical trials on stem cell therapy of ischemic heart disease.

Heparinized PGA host-guest hydrogel loaded with paracrine products from electrically stimulated adipose-derived mesenchymal stem cells for enhanced wound repair

The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-guest hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.

Stroma-epithelium crosstalk in prostate cancer

The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-J3, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-l, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor （AR）, and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.

Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats

This study aimed to explore the therapeutic effects of adipose-derived stem cells （ADSCs）-based microtissues （MTs） on erectile dysfunction （ED） in streptozotocin （STZ）-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ （60 mg kg-1）, and 8 weeks later, the determined diabetic rats randomly received intracavernous （IC） injection of phosphate buffer solution （PBS）, ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure （ICP）, histopathological changes in corpus cavernosum （CC）, and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor （VEGF）, nerve growth factor （NGF）, and tumor necrosis factor-stimulated gene-6 （TSG-6）. MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase （nNOS） expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.