Mesenchymal stem cells

Humans are keenly aware of their mortality. Given a limited time what we do with our life is a reflection of knowledge of our mortality. In 2009 the Nobel prize in medicine to Jack W Szostak, Elizabeth Blackburn, Carol W Greider for their work on Telomerase and scientific research exploded in this area. Telomere protect chromosome ends the Telomerase enzyme maintains Teleomere length. This activity of Telomerase is essential in aging and stem cells and achieving longer life spans. Telomerase is expressed in 85% of human cancer cell lines, but its enzymatic activity is not detectable in most human somatic cells which constitute the vast majority of the cells in the human body. There is a need for increased telomerase activity in stem cells for use in the treatment of therapies where there is an active role for telomerase. Umbilical Cord Blood (UCB) provides an attractive source of stem cells for research and therapeutic uses. Work shown here characterizes the gene expression changes from Umbilical cord cells differentiate toward telomerase on treatment with Metadichol ®. Metadichol ® is a nanoemulsion of long-chain alcohols that is nontoxic. It is a mixture of long-chain alcohols derived from food. The work presented here is about the effect of Metadichol ® on Telomerase expression profile in Umbilical cord cells. Our results using q-RT-PCR show increases of mRNA telomerase expression by Sixteen-fold at one picogram but down-regulates expression at higher concentrations of 100 pg, 1 ng, 100 ng and one microgram per ml concentration. Western blot studies showed expression of Telomerase protein which is slightly higher than control at one picogram, i.e., Telomerase protein expression continues at replacement level. Since it is devoid of toxic effects, it can be directly tested on humans and is in use today as an immune boosting supplement. Metadichol ® increases expression of Klotho an anti-aging gene expression in cancer cell lines by Four to Tenfold , and Klotho gene has been documented to inhibits the growth of cancer cells. Metadichol ® also inhibits TNF, ICAM1, CCL2, and BCAT1 which that is associated with proliferation in yeast and increased metastatic potential in human cancers. It paves the way for safe clinical testing and research and study of Telomerase biology and its use in humans.

Bovine adipose-derived stem cells were obtained from the subcutaneous abdominal adipose tissue. The cells were cultured by the modified tissue-explants method developed in our laboratory, and then analyzed using optical microscopy and flow cytometry. These cells were able to replicate in our cell culture conditions. cell Flow cytometry showed that bovine adipose-derived stem cells expressed mesenchymal stem cell markers (CD73 and CD90). Meanwhile, haematopoietic markers (CD45 and CD34) are absent from bovine adipose-derived stem cells. We also induced their adipogenic differentiation in vitro.

Over the past few years, substantial progress has been made in the field of stem cell regeneration of the intervertebral disc. Autogenic mesenchymal stem cells in animal models can arrest intervertebral disc degeneration or even partially regenerate it and the effect is suggested to be dependent on the severity of degeneration. Mesenchymal stem cells (MSCs) are able to escape alloantigen recognition which is an advantage for allogenic transplantation. A number of injectable scaffolds have been described and various methods to pre-modulate MSCs’ activity have been tested. In future, work will need to address the use of mesenchymal stem cells in large animal models and the fate of the implanted mesenchymal stem cells, particularly in the long term, in animals. This review examines the state-of-the-art in the field of stem cell regeneration of the intervertebral disc, and critically discusses, with scientific support, the issues involved, before stem cells could be used in human subjects.

Stroke is the leading cause of neurological disability in adults worldwide and involves the significant impairment of sensory-motor function caused by cerebral ischemia and subsequent neuronal death. Owing to a lack of medical or surgical treatments to improve neurological function and neurogenesis, chronic stroke places a huge burden on patients, their families, and society. Over the past twenty years, increasing evidence from translational and clinical research has demonstrated the potential effectiveness of hematopoietic growth factors and stem cell administration or transplantation in the treatment of stroke. In particular, these studies have included granulocyte colony-stimulating factor, mesenchymal stem cells, autologous CD34 + peripheral blood stem cells, umbilical cord blood stem cells, and autologous adipose-derived mesenchymal stem cells. It is therefore important to consider the safety of these putative therapies whilst achieving the maximum benefit for patients with chronic stroke in terms of the route of administration and stem cell numbers. In this review, we discuss current evidence and the progress that has been made in our hospital, which paves the way for the next neurogenesis therapy for chronic stroke.

ABSTRACTMultipotent mesenchymal stem cells (MSCs) are special kind of stem cells which originate from mesenchyme. These cells can be used as an imperativetool to study reproductive toxicity, carcinogenicity, mutagenicity, genotoxicity, and pharmacokinetics. This novel system may reveal toxicantinducedetiology, decipher detailed understanding on molecular mechanisms of toxicants induced pathways and also enumerate the safe dose ofan investigational product. Hence, this could ultimately replace, improve or overtake current predictive models in toxicology. The particular reviewdescribes the utilization of MSCs in different field of toxicological and pharmacological research.Keywords: Mesenchymal stem cells, Toxicant, Etiology, Pharmacokinetics.

Background: Type II diabetes mellitus (T2DM) is known as non-insulin dependent diabetes mellitus. Insulin impairment and insulin resistance are the major causes of type II diabetes mellitus. People with T2DM are more prone to macro-vascular and micro vascular impediments. Adult Autologous Adipose derived stem cells (ADSC) hold potential to develop into multilineages and they can secrete numerous growth factors that can regenerate the damaged neighboring cells. The chronic wound healing processes and diabetes-associated complications are reported to be treated by using stem cells by revascularization and by promoting the micro vascular remodeling. Objective: To evaluate the safety and efficacy of Adipose derived autologous stem cells and PRP in patients suffering from Type 2 Diabetes Mellitus (T2DM). Methods: We reported three cases aged 50, 69 and 72 years suffering from T2DM since 20, 10 and 20 years respectively. They were treated with Adult autologous ADSC and Platelets Rich Plasma (PRP). Results: Over a follow up of twelve months significant control in glycemia as well as stable glycosylated hemoglobin with decrease in pain on Visual Analogous scale (VAS) score has been observed.

Objective
We aimed to identify the differentially expressed proteins (DEPs) and functional differences between exosomes derived from mesenchymal stem cells (MSCs) derived from umbilical cord (UC) or adipose tissue (AD).

Materials And Methods
In this experimental study, the UC and AD were isolated from healthy volunteers. Then, exosomes from UC-MSCs and AD-MSCs were isolated and characterized. Next, the protein compositions of the exosomes were examined via liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by evaluation of the DEPs between UC-MSC and AD-MSC–derived exosomes. Finally, functional enrichment analysis was performed.

Results
One hundred and ninety-eight key DEPs were identified, among which, albumin (ALB), alpha-II-spectrin (SPTAN1), and Ras-related C3 botulinum toxin substrate 2 (RAC2) were the three hub proteins present at the highest levels in the protein-protein interaction network that was generated based on the shared DEPs. The DEPs were mainly enriched in gene ontology (GO) items associated with immunity, complement activation, and protein activation cascade regulation corresponding to 24 pathways, of which complement and coagulation cascades as well as platelet activation pathways were the most significant.

Conclusion
The different functions of AD- and UC-MSC exosomes in clinical applications may be related to the differences in their immunomodulatory activities.

62 on 100 yıl içerisinde insanların yaşam beklentisi ve sosyal hayata katkıları de-ğişmiştir. Yaşlı populasyon fiziksel ve mental olarak daha aktif olmakla bera-ber yaşam süreleri de artmış bulunmaktadır. Genç populasyonun ise spor ile ilişkisi giderek atmıştır ve spor yaralanmaları ile olan maruziyet oranı da dolayısla artmıştır. Ortopedi diğer tıp dalları arasında teknolojiyi en iyi kullanan alanlardan biri olmasına rağmen özellikle gençlerde ki ortopedik sorunlar için biyolojik çö-zümlere ihtiyaç vardır. Son 30 yıl içerisinde biyomateryaller, implantlar, eklem re-konstrüksiyonu için kullanılan protezler, enstrümanlar, navigasyon ve robotik sistemler daha iyi bir düzeye gelmişlerdir. Ancak imlantların bir sağkalım süresi vardır ve ister gevşeme olsun ister başka bir nedene bağlı olsun implant veya pro-tez yetmezliği ikincil müdahalere neden olmaktadır. Gelecek kendini yenileyebi-len doku ve organ çözümlerinde aranmaktadır. Bu gelişime en yakın durum ise kendini yenileyebilen ve diğer hücrelere diferansiye olabilme kapasitesine sahip kök hücre kullanımında gibi gözükmektedir. Kök hücreler tiplerine göre pluripotent veya multipotent olabilmektedirler. Sadece embrio totipotenttir, birçok doku tipine diferansiye olma kapasitesine sa-hiptirler. Ancak yetişkin kök hücrelerin diferansiye olma kapasiteleri genelde sı-Ortopedik Hastalıklarda Mezenkimal Kök Hücre Uygulamaları Ö ÖZ ZE ET T Mezenkimal kök hucre tedavisinin ortopedide kullanımı ile ilgili ilk çalışmalar çok uzun yıl-lara dayanmaktadır. Hayvan deneylerinde kıkırdak, menisküs, tendon ve intervertebral disk iyi-leşmesi üzerine olan etkileri görülmüştür. İlk bilgiler erken kıkırdak iyileşmesi üzerinde görülmüş ve sonuçlar yüz güldürücü olmuştur. Bu bulgulara dayanarak doku mühendisliği ortopedide me-zenkimal kök hücre tedavisini daha da geliştirmiştir. A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Erişkin kök hücreler; mezenkimal kök hücreler; ortopedi; differensiasyon A AB BS S T TR RA AC CT T The first studies about use of mesenchymal stem cell in orthopedics based on many years. In animal experiments, it was seen as effects on cartilage healing, tendon and meniscus repair and intervertebral disc treatment. Early results were seen on primarily cartilage repair and these results have been satisfactory. Based on mentioned findings, tissue engineering has developed even further of stem cell treatment in orthopedics.

The STRO-1 antibody can be used as a single reagent to isolate human bone marrow stromal stem cells (BMSSC), owing to its restricted specificity to a cell surface molecule expressed by clonogenic BMSSC, with little or no reactivity to hematopoietic stem/progenitor populations or mature stromal elements. The present protocol uses a combination of two different immunoselection methodologies in an attempt to generate highly purified preparations of BMSSC. This process involves the initial isolation of a minor subpopulation of bone marrow mononuclear cells (approx 10%) expressing the STRO-1 antigen, by means of magnetic activated cell sorting. Dual-color fluorescence activated cell sorting is then used as a secondary step to further purify the rare STRO-1bright expressing fraction that contains all of the colony-forming BMSSC, based on their co-expression of a secondary cell surface marker, CD106 (VCAM-1).

The osteocyte is believed to act as the primary sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on bones throughout life. Alterations in local bone tissue composition and structure arising during osteoporosis likely disrupt the local mechanical environment of these mechanosensitive bone cells, and may thereby initiate a mechanobiological response. However, due to the difficulties in directly characterising the mechanical environment of bone cells in vivo, the mechanical stimuli experienced by osteoporotic bone cells are not known. The global aim of this thesis is to discern the in vivo mechanical environment of the osteocyte, both in healthy bone tissue and during the disease of osteoporosis.
The first study of this thesis involved the development of 3D finite element models of osteocytes, including their cell body and the surrounding pericellular matrix (PCM) and extracellular matrix (ECM), using confocal images of the lacunar-canalicular network. These anatomically representative models demonstrated the significance of geometry for strain amplification within the osteocyte mechanical environment. A second study employed fluid-structure interaction (FSI) modelling to investigate the complex multi-physics environment of osteocytes in vivo. These models built upon the anatomically representative models developed in the first study, and FSI methods were used to simulate loading-induced interstitial fluid flow through the lacunar-canalicular network. Interestingly, the in vivo mechanical stimuli (strain and shear stress) predicted using these computational approaches were above thresholds known to elicit osteogenic responses from osteoblastic cells in vitro, and thereby provide a novel insight into the complex multi-physics mechanical environment of osteocytes in vivo.
The third study of this thesis sought to experimentally characterise the strain environment of osteoblasts and osteocytes under physiological loading conditions in healthy and osteoporotic bone, using a rat model of osteoporosis. A custom-designed loading device compatible with a confocal microscope was constructed to apply strains to fluorescently stained femur samples from normal and ovariectomised rats. Confocal imaging was performed simultaneously during loading and digital image
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correlation techniques were used to characterise cellular strains from the images acquired. These results suggested that the mechanical environment of osteoblasts and osteocytes is altered during early-stage osteoporosis, and it is proposed that a mechanobiological response restores the homeostatic mechanical environment by late-stage osteoporosis. A final study applied these results as inputs for the developed computational models to investigate whether changes in tissue properties, lacunar-canalicular architecture or amplification mechanisms during osteoporosis could explain the altered mechanical stimulation of osteocytes observed. The findings of this study shed new light on the osteocyte mechanical environment in both healthy and osteoporotic bone, elucidating a possible mechanobiological relationship between increases in strain stimulation of the osteocyte and subsequent increases in mineralisation of bone tissue as key events in the progression of osteoporosis.
Together, the studies in this thesis provide a novel insight into the closed mechanical environment of the osteocyte. Using both computational and experimental methods, the mechanical stimuli that osteocytes experience under physiological loading in vivo, in both healthy and osteoporotic bone, were elucidated. In particular, the research in this thesis provides a missing mechanobiological link in the temporal development of post-menopausal osteoporosis, and the information gained from this body of work may inform future treatments for osteoporosis.

Hematopoiesis is the process in which all Blood lineages are produced from Hematopoietic Stem cells. Through series of Progenitor cells, Hematopoietic stem cells produce a large number of Adult Stem cells. Hematopoietic Stem cells have the ability of self-renewal and self-division This Divisional event results in the Differentiation of Hematopoietic Stem cells into-Lymphocytes, Granulocytes, Monocytes, etc. Progenitor cells also contain cells that act as our body's Defense mechanism. This Always active defense mechanism consists of T cells, B cells, and Natural Killer cells. These cells work together to fight against any viruses or any pathogen and destroy them or exclude them out of the body. By understanding the Hematopoietic process and Defense mechanism, development has been done in the formation of new therapies for curing specific diseases. The basic concept of Stem cell production and its classification are defined here. This paper includes the concept of the production of Progenitor cell lineages which are classified as Lymphoid Progenitor cells and Myeloid Progenitor cells. Here we discuss the Embryonic development and classification of each blood lineages.

The biomolecule conjugated macroporous hydrogels have been particularly investigated in
the field of bioseparation, biocatalysts, bioreactor, cell therapy, tissue regeneration and
environmental applications. This review focuses on different types of biological molecules
that have been conjugated on macroporous hydrogels. A variety of techniques are available
for the fabrication of macroporous hydrogels and attachment of biomolecules. The natural
polymers, ECM components, growth factors, peptides and proteins have been widely used for
the functionalization of macroporous hydrogels in various biomedical applications. The
major areas benefited by the incorporation of these biomolecules are separation of cells and
biomolecules (e.g. antibody), tissue repair and regeneration (e.g. peptides and ECM
molecules), biocatalysts (e.g. enzyme) and controlling of environmental pollution.
Additionally, functionalization of macroporous hydrogels with chemical drugs have
demonstrated their controlled drug release capabilities. Moreover, clinically available
biofunctionalized macroporous polymeric products have been briefly discussed.

Neurodegeneration is a general term for the progressive loss of structure and/ or function of neurons, gives rise to dysfunction or death of neurons. Neurodegenerative diseases including Alzheimer´s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinal cord injury (SCI) and brain ischemia (BI) occur as a result of neurodegenerative processes leading to different degrees of paralysis and loss of sensation and cognition in the patients. Unfortunately, no successful cure for neurodegenerative disorders has been developed so far, and most of the currently available pharmacological therapies are mainly palliative. In recent years, stem cells have provided a great opportunity to develop potentially powerful innovative strategies to cure neurodegenerative diseases. Stem cells transplantation is capable of restoring injured neuronal tissue by replacement of the damaged cells via using directly differentiated cells or by protecting of existing healthy neurons and glial cells from further damage, or by repairing through providing a conductive environment in favor of regeneration. Here we have brought together some of these examples, discuss possible therapeutic means using different types of stem cells, mainly adult stem cells (ASCs), to treat neurodegenerative diseases.

The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, which aim to improve ease of use and cost-effectiveness, are progressively explored. The use of MSCs in cartilage repair makes it possible to develop single-stage cell-based therapies. However, true single-stage procedures rely on one intervention, which will limit cell sources to fraction concentrates containing autologous MSCs or culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic cells can safely be applied, but clinical studies are still ongoing and little information on clinical outcome is available. Further development of cell-based therapies may lead to clinical-grade, standardized, off-the-shelf products with easy handling for orthopedic surgeons. Although as of yet no preclinical or clinical studies are ongoing which explore the use of induced pluripotent stem cells for cartilage repair, a good manufacturing practice-grade induced pluripotent stem cell line might become the basis for such a product in the future, providing that cell fate can be controlled. The use of stem cells in clinical trials brings along new ethical issues, such as proper controls and selecting primary outcome measures. More clinical trials are needed to estimate detailed risk-benefit ratios and trials must be carefully designed to minimize risks and burdens for patients while choosing outcome measures that allow for adequate comparison with results from similar trials. In this review, we discuss the different aspects of new stem cell-based treatments, including safety and ethical issues, as well as provide an overview of current clinical trials exploring these approaches and future perspectives.

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

Adipose tissue is accessible with minimally invasive procedures, is abundant, and is replenishable. It consists of a heterogeneous cell population including preadipocytes, mature adipocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, resident macrophages, and cells composing the stromal vascular fraction. This fraction contains multipotent cells with the same mesenchymal origin and similar biological and immunological characteristics of bone marrow stroma. On the other hand, adipose-derived stromal cells are easier to harvest and culture in comparison to bone marrow-derived ones. The authors discuss the microenvironment where are the stem cells is the niche, adipose tissue, and adipose tissue-derived stromal cell transplant for the treatment of epithelial pathologies, wound healing, diabetic foot, and other disorders.

We previously demonstrated that subretinal injection (SRI) of isogenic mesenchymal stem cells (MSCs) reduced the severity of retinal degeneration in Royal College of Surgeons rats in a focal manner. In contrast, intravenous MSC infusion (MSC IV) produced panoptic retinal rescue. By combining these treatments, we now show that MSC IV supplementation potentiates the MSC SRI-mediated rescue of photoreceptors and visual function. Electrophysiological recording from superior colliculi revealed 3.9-fold lower luminance threshold responses (LTRs) and 22% larger functional rescue area from combined treatment compared with MSC SRI alone. MSC IV supplementation of sham (saline) injection also improved LTRs 3.4-fold and enlarged rescue areas by 27% compared with saline alone. We confirmed the involvement of MSC chemotaxis for vision rescue by modulating C-X-C chemo-kine receptor 4 activity before MSC IV but without increased retinal homing. Rather, circulating platelets and lymphocytes were reduced 3 and 7 days after MSC IV , respectively. We demonstrated MSC SRI-mediated paracrine support of vision rescue by SRI of concentrated MSC-conditioned medium and assessed function by electroretinography and optokinetic response. MSC-secreted pep-tides increased retinal pigment epithelium (RPE) metabolic activity and clearance of photoreceptor outer segments ex vivo, which was partially abrogated by antibody blockade of trophic factors in concentrated MSC-conditioned medium, or their cognate receptors on RPE. These data support multimodal mechanisms for MSC-mediated retinal protection that differ by administration route and synergize when combined. Thus, using MSC IV as adjuvant therapy might improve cell therapies for retinal dystrophy and warrants further translational evaluation. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1–14 SIGNIFICANCE Despite hundreds of clinical trials, just one stem cell treatment has been approved for the U.S. market. Additional treatments nearing clinical acceptance use bone marrow mesenchymal stem cells for in-flammatory and immune-related conditions. This is because safety has been established over decades of testing, and cell transplants prolong life-saving organ and tissue grafts. In the present study, the intravenous delivery of mesenchymal stem cells enhanced the vision rescue from primary cell grafts into diseased retinae. This combined transplant strategy could improve functional outcomes for cell-based therapies, expand their utility, and expedite their clinical acceptance.

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Mesenchymal stem/stromal cells (MSCs) display a variety of therapeutically relevant effects, such as the induction of angiogenesis, particularly under hypoxic conditions. It is generally recognized that MSCs exert their effects by secretion of paracrine factors and by stimulation of host cells. Furthermore, there is increasing evidence that some therapeutically relevant effects of MSCs are mediated by MSC-derived extracellular vesicles (EVs). Since our current knowledge on MSC-derived EVs released under hypoxic conditions is very limited, we aimed to characterize MSC-derived EVs from normoxic vs. hypoxic conditions (5% O 2). Adipose-derived MSCs were grown under normoxic and hypoxic conditions, and EVs were analyzed by flow cytometry using lactadherin as a marker for EVs exposing phosphatidylserine, CD63 and CD81 as EV markers, as well as CD73 and CD90 as MSC surface markers. Particle concentration and size distribution were measured by nanoparticle tracking analysis (NTA), and the EV surface antigen signature was characterized using bead-based multiplex flow cytometry. Furthermore, we evaluated the potential of MSC-derived EVs obtained under hypoxic conditions to support angiogenesis using an in vitro assay with an hTERT-immortalized human umbilical vein endothelial cell (HUVEC) line. Proliferation and viability of MSCs were increased under hypoxic conditions. EV concentration, size, and surface signature did not differ significantly between normoxic and hypoxic conditions, with the exception of CD44, which was significantly upregulated on normoxic EVs. EVs from hypoxic conditions exhibited increased tube formation as compared to normoxic EVs or to the corresponding supernatants from both groups, indicating that tube formation is facilitated by EVs rather than by soluble factors. In conclusion, hypoxia conditioned MSC-derived EVs appear to be functionally more potent than normoxic MSC-derived EVs regarding the induction of angiogenesis.