Muscle Blood Vessels Research Articles

Angiomyolipoma Suspected to be the Lobular Capillary Hemangioma in the Nasal Cavity.

Angiomyolipoma (AML), composed of smooth muscle cells, blood vessels, and adipose tissues, belongs to a family of tumors originating from perivascular epithelioid cells. Angiomyolipoma most commonly arises in the kidney but is extremely rare in the nasal cavity. Angiomyolipoma is classified into hepatorenal and mucocutaneous AML. Mucocutaneous AML is defined as AML originating from the skin and nasopharyngeal mucosa. Mucocutaneous AML should be distinguished from hepatorenal AML because hepatorenal AML has a malignant potential. Moreover, mucocutaneous AML must be considered in the differential diagnosis for unilateral nasal mass despite being a rare disease. The authors present the case of a 70-year-old woman with mucocutaneous AML who complained of right epistaxis. Although she had a history of hypertension and acute myocardial infarction, it was not related to tuberous sclerosis. Endoscopic examination revealed a round and reddish mass protruding from the right inferior meatus. She underwent endoscopic resection without complications. She had no recurrence for 15 months.

When benign turns aggressive: renal angiomyolipoma with renal vein invasion

Angiomyolipoma (AML) is the most common benign kidney tumor, made up of fat, smooth muscle, and abnormal blood vessels. It represents 0.3-3% of kidney tumors and is more common in women. AMLs are typically diagnosed via computed tomography (CT) or magnetic resonance imaging (MRI), with most being asymptomatic and requiring no treatment. However, larger or symptomatic AMLs can cause hematuria, flank pain, or bleeding, necessitating treatments like selective arterial embolization, partial nephrectomy, or active surveillance. Recent studies question the traditional 4 cm intervention threshold, suggesting that larger AMLs may be safely monitored based on individual risk factors. This case report discusses a 47-year-old woman with a 4.1×2.1 cm AML with renal vein invasion, treated successfully with laparoscopic nephrectomy. The findings highlight the need for personalized treatment strategies considering tumor characteristics and patient factors, and emphasize the importance of ongoing renal function monitoring.

Deep Neural Network Framework for Predicting Cardiovascular Diseases from ECG Signals

Introduction: Cardio Vascular Disease (CVD), a primary cause of death worldwide, includes a variety of heart-related disorders like heart failure, arrhythmias, and coronary artery disease (CAD), where plaque buildup narrows the heart muscle's blood vessels and causes angina or heart attacks. Genetics, congenital anomalies, bad diet, lack of exercise, smoking, and chronic diseases including hypertension and diabetes can cause cardiac disease. Method: The symptoms can range from chest pain and shortness of breath to exhaustion and palpitations and diagnosis usually involves a medical history, physical examination, and electrocardiograms (ECGs), and stress testing. Lifestyle adjustments, medicines, angioplasty, and bypass grafts or heart transplants are possible treatments. Preventive measures include healthy living, risk factor management, and frequent checkups, which are few measures, whereas advanced algorithms can analyze massive volumes of ECG and MRI data to find patterns and anomalies that humans may overlook. Results: The deep learning models increase arrhythmia, coronary artery disease, and heart failure diagnosis accuracy and speed. They enable predictive analytics, early intervention, and personalized treatment programs, increasing cardiac care results. The proposed DNN model consists of a 3-layer architecture having input, hidden, and output layers. In the hidden layer, 2 layers, namely, the dense layer and batch normalization layer are added to enhance its accuracy. Conclusion: Three different optimizers namely Adam, AdaGrad, and AdaDelta are tested on 50 epochs and 32 batch sizes for predicting cardiovascular disease. Adam optimizer has the highest accuracy of 85% using the proposed deep neural network.

Downregulation of Genes for Skeletal Muscle Extracellular Matrix Components by Cisplatin

The extracellular matrix (ECM) in skeletal muscle is involved in a variety of physiological functions beyond the mechanical support of muscle tissue, nerves, and blood vessels; however, the role of the ECM in skeletal muscle remains unclear. There is little information regarding changes in the expression of factors comprising the ECM during cisplatin-induced muscle atrophy. In the present study, we examined the changes in gene expressions for skeletal muscle extracellular matrix components in skeletal muscle during cisplatin-induced muscle atrophy. Intraperitoneal administration of cisplatin caused muscle atrophy in mice and during this cisplatin-induced muscle atrophy, the expression of many procollagen genes (Col1a1, Col1a2, Col3a1, Col4a1, Col5a1, and Col5a2), elastin (Eln), fibronectin (Fn1), Laminin (Lama1, Lama2, and Lamb1) decorin (Dcn), heparan sulphate proteoglycans (Hspg2) and integrin (Itgb1) constituting the ECM was suppressed. Additional studies are needed to elucidate the pathological significance and mechanisms of reduced gene expression of ECM components associated with cisplatin-induced muscle atrophy.

3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration.

Hydrogel scaffolds have numerous potential applications in the tissue engineering field. However, tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties. Inspired by Chinese ramen, we propose a universal fabricating method (printing-P, training-T, cross-linking-C, PTC & PCT) for tough hydrogel scaffolds to fill this gap. First, 3D printing fabricates a hydrogel scaffold with desired structures (P). Then, the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance (T). Finally, the training results are fixed by photo-cross-linking processing (C). The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66MPa (622-fold untreated) and have excellent biocompatibility. Furthermore, this scaffold possesses functional surface structures from nanometer to micron to millimeter, which can efficiently induce directional cell growth. Interestingly, this strategy can produce bionic human tissue with mechanical properties of 10kPa-10MPa by changing the type of salt, and many hydrogels, such as gelatin and silk, could be improved with PTC or PCT strategies. Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers, blood vessels, and nerves within 4weeks, prompting the rapid regeneration of large-volume muscle loss injuries.

Endoscopic minimally invasive treatment of congenital muscular torticollis in children

BackgroundThis study aimed to investigate the clinical efficacy of minimally invasive endoscopic treatment of children with congenital muscular torticollis (CMT).MethodsIn total, 72 children (41 male, 31 female) with CMT who underwent endoscopic surgery at the Department of Orthopedics, Xi’an Children’s Hospital, between January 2021 and January 2023 were included. Their mean age was 54 ± 36.1 (range, 12–141) months. Of these, 29 (40.3%) cases involved the left side while 43 (59.7%) involved the right side. Preoperative preparation involved precise body surface markings of the sternocleidomastoid muscle(SCM), clavicle, and important nerve and blood vessels, followed by the establishment of surgical channels through passive separation techniques. An arthroscope and a low-temperature plasma knife were utilized for accurate localization and surgical release of the clavicular and sternal heads of the SCM. The duration of surgery, blood loss, postoperative hospital stay, neck range of motion measurements, and any intraoperative or postoperative complications were analyzed using the rank sum test. Cervical and thoracic braces were applied for three months postoperatively, with follow-up assessments conducted using Cheng’s scoring system.ResultsAll patients successfully underwent endoscopic surgery, without the need for conversion to open surgery. No intra- or postoperative complications were observed. The average surgical duration was 56.4 ± 15.7 min, with minimal intraoperative bleeding (1–5 mL) and no need for blood transfusion. The mean postoperative hospital stay was 2.7 ± 0.8 days. Over a mean follow-up period of 22.2 ± 5.5 (range, 14–32) months, significant improvements were observed in neck rotation (from 20.2° [17.7° to 25°] to only 3.6° [2° to 6.7°]) and lateral flexion (from 19° [17° to 22.6°] to only 3° [2° to 7.8°]) restrictions (p < 0.05). According to Cheng’s scoring system, 70 (97.2%) patients achieved excellent or good clinical outcomes, while 2 (2.8%) had average outcomes. The torticollis deformity was corrected during the follow-up period, and all surgical incisions healed without noticeable scarring.ConclusionEndoscopic release is a safe, effective, and minimally invasive treatment option for CMT in children.

Musculoskeletal Disorders (MSDs) Among Lecturers and Employees During Pandemic Era in Universitas Pekalongan

Musculoskeletal Disorders (MSDs) comprise a spectrum of symptoms involving muscle tissue, tendons, ligaments, cartilage, nervous, system, bone structures, and blood vessels. MSDs cause pain, numbness, tingling, swelling, stiffness, shaking, sleep disturbances, and burning sensations. Due to the impact of Covid-19, the change of the work from the office to be work from home is a concern as it may exacerbate. This study aimed to describe symptoms of MSDs among lecturers and employees during pandemic era in Universitas Pekalongan. This is a descriptive study with crosssectional design. It involved 36 respondents including lecturers and employees of Universitas Pekalongan. Each respondent was asked to fulfill the observation checklist that examined symptom of pain from head to toe which divided into 28 parts of the body. Results of this study revealed that majority respondents of this study aged range from 31-40 years old (41.7%), gender of male (52.8%), type of work was employees (52.8%), and have the length or work about 0-5 years (25.0%). The results show that the five highest region of the body that experienced MSDs in level “Pain” were upper neck, lower neck, back, waist, and buttock ranging from 11.1% to 16.7%. Whereas, there was only 2.8% respondents reported of feeling “Extremely Pain” in region left knee. Employees who worked in administration were more in a monotonous position with computer work equipment. Meanwhile, lecturers were worked online during the pandemic and required to have a sedentary life where they carry out almost all of their activities monotonously in a sitting position in front of the computer. It recommended that the institutions should pay more attention towards strategies of occupational health among lecturers and employees in Universitas Pekalongan. Keywords: MSDs, musculoskeletal disorders, occupational health, universitas pekalongan

The expression of intermediate filaments in the abomasum of ruminants: A comparative study.

Intermediate filaments (IFs) are key molecular factors of the cell and have been reported to play an important role in maintaining the structural integrity and functionality of the abomasum. This study was designed to determine the regional distribution, cellular localization and expression of several IFs, including CK8, CK18, CK19, vimentin, desmin, peripherin and nestin, as well as the connective tissue component laminin, in the bovine, ovine and caprine abomasa. Immunohistochemical analyses demonstrated varying levels of expression of CK8, CK18, CK19, vimentin, desmin, nestin, peripherin and laminin in the bovine, ovine and caprine abomasa. CK8 immunoreactions were particularly evident in the luminal and glandular epithelia of the glands found in the abomasal cardia, fundus and pylorus in all three species. In the bovine abomasum, CK18 immunoreactions were stronger in the parietal cells, compared to the chief cells. In the abomasum of all three species, the smooth muscle as well as the smooth muscle cells of the vascular media in the cardiac, fundic and pyloric regions showed strong immunoreactivity. In all three species, the cardiac, fundic and pyloric regions of the abomasum showed strong peripherin and nestin immunoreactions in the luminal and glandular epithelial cells, stromal and smooth muscle cells, nervous plexuses and blood vessels. The expression patterns of IFs and laminin in the ruminant abomasum suggest that these proteins play a structural role in the cytoskeleton and are effective in maintaining abomasal tissue integrity and stability.

Efektivitas Terapi Relaksasi Nafas Dalam untuk Menurunkan Nyeri Akut pada Pasien Fraktur di RSUD Hajjah Andi Depu

A fracture or fracture is a disruption of the continuity of both total, partial bone tissue that can affect the long bone, joints of muscle tissue and blood vessels causing injury to the movement of the limb. Each individual will adapt to the changes that occur. At RSUD Hajja Andi Depu, the number of fractural patients by 2022 reached 157 people. The study aims to investigate the effectiveness of giving deep breath relaxation techniques to patients with fractures with moderate pain. The research project uses one group pre-post test design with a total sample of 22 respondents with purposive sampling techniques. Pain analysis is measured using the Numerc Rating scale. The study used univariate and bivariate analysis. From the results of the study showed the average prior to the inhalation technique is 6.27 and the average result after the given inhaling technique is 3.54. The bivariate result obtained p-value =0,001 &lt;0,05 so it can be concluded that the action of breathing relaxation technique in effective in reducing the intensity of pain in patients fractures.

Coincidence between the distribution of myofascial trigger points and the presence of blood vessels in the gastrocnemius muscle: Implications for invasive procedures.

The gastrocnemius venous system presents different anatomical variants. There have been described four locations of myofascial trigger points (MTrPs) in this muscle. However, no studies have analyzed the coincidence between vessels and MTrPs present in the gastrocnemius. Therefore, the main objective was to study the anatomical variability of the venous system by ultrasound and its coincidence with the location of the MTrPs. A total of 100 lower limbs were studied. The gastrocnemius vessels were analyzed one by one by sector (medial, central, and lateral), quantifying the number of vessels, their distribution, and the coincidence with MTrPs. All muscle heads showed at least one vessel per section. A large variability was observed, from one to eight vessels per muscle head, with the most frequent number being three in the gastrocnemius medialis and two in the gastrocnemius lateralis. In all cases, the location of the vessels coincided with the MTrPs. The proximal gastrocnemius venous pattern is very variable between subjects in number of vessels and distribution, which has made it impossible to define a "safe" approach window for invasive procedures without ultrasound guidance. The coincidence between the clinical location of MTrPs of the gastrocnemius and the presence of vessels is total.

Dynamic injectable tissue adhesives with strong adhesion and rapid self-healing for regeneration of large muscle injury

Wounds often necessitate the use of instructive biomaterials to facilitate effective healing. Yet, consistently filling the wound and retaining the material in place presents notable challenges. Here, we develop a new class of injectable tissue adhesives by leveraging the dynamic crosslinking chemistry of Schiff base reactions. These adhesives demonstrate outstanding mechanical properties, especially in regard to stretchability and self-healing capacity, and biodegradability. Furthermore, they also form robust adhesion to biological tissues. Their therapeutic potential was evaluated in a rodent model of volumetric muscle loss (VML). Ultrasound imaging confirmed that the adhesives remained within the wound site, effectively filled the void, and degraded at a rate comparable to the healing process. Histological analysis indicated that the adhesives facilitated muscle fiber and blood vessel formation, and induced anti-inflammatory macrophages. Notably, the injured muscles of mice treated with the adhesives displayed increased weight and higher force generation than the control groups. This approach to adhesive design paves the way for the next generation of medical adhesives in tissue repair.

Primary ovarian leiomyoma in a patient with uterine leiomyoma

A small, unilateral tumor. Most ovarian leiomyomas (OLM) are benign, but can range from benign to borderline with malignant degeneration. In many patients, OLM are asymptomatic and are detected accidentally during surgery. In rare cases, OLM can be accompanied by severe symptoms as their size increases. This situation requires differentiation these formations from malignant ovarian tumors, which is more often observed during the perimenopausal and menopausal periods. Being discussed that the source of OLM is smooth muscle blood vessel cells, so more undiagnosed small asymptomatic OLMs can be expected. This article presents a clinical case of OLM in a 39-year-old woman operated for uterine myoma. In the case we presented the coexistence of uterine fibroids and ovarian leiomyoma, which subsequently received diagnostic confirmation.

Transmembrane stem factor nanodiscs enhanced revascularization in a hind limb ischemia model in diabetic, hyperlipidemic rabbits

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia.

Decoding the forces that shape muscle stem cell function.

Skeletal muscle is a force-producing organ composed of muscle tissues, connective tissues, blood vessels, and nerves, all working in synergy to enable movement and provide support to the body. While robust biomechanical descriptions of skeletal muscle force production at the body or tissue level exist, little is known about force application on microstructures within the muscles, such as cells. Among various cell types, skeletal muscle stem cells reside in the muscle tissue environment and play a crucial role in driving the self-repair process when muscle damage occurs. Early evidence indicates that the fate and function of skeletal muscle stem cells are controlled by both biophysical and biochemical factors in their microenvironments, but much remains to accomplish in quantitatively describing the biophysical muscle stem cell microenvironment. This book chapter aims to review current knowledge on the influence of biophysical stresses and landscape properties on muscle stem cells in heath, aging, and diseases.

Effect of neoadjuvant endocrine therapy on the acoustic environment in tissue of prostate cancer: a study of histopathological characteristics.

Neoadjuvant endocrine therapy (NET) of prostate cancer (PCa) may alter the tissue acoustic environment (AET). The structure of tissue is an important factor affecting AET. The aim is to analyze changes in tissue structures after NET in PCa, focusing on calcifications, smooth muscle cells, and blood vessels. We collected 40 patients diagnosed with PCa by pathological examination between October 2020 and December 2022. Twenty patients who underwent radical prostatectomy (RP) after NET were designed as the test group. Twenty patients without NET were assigned to the control group. Calcifications, smooth muscle cells and blood vessels were observed by hematoxylin-eosin (HE) staining and Van Gieson (VG)-special staining respectively. Then the amount and acreage of calcified tissue, the number of smooth muscle cells and different types of blood vessels were quantitatively analyzed. There was a subtle increase in the number (P=0.001) and the area (P<0.001) of calcification after NET. The total number of smooth muscle cells was significantly higher than that without NET (P<0.001). NET resulted in significantly fewer veins compared to those without NET (P<0.001). There was a little increase in the number of arteries after NET (P=0.001). The number of veins decreased was much greater than the number of arteries increased resulting in significantly fewer total vessels after NET (P<0.001). NET can lead to changes in calcifications, smooth muscle cells, and blood vessels within PCa tissues, which may cause alterations in AET.

Hepatic Angiomyolipoma: A Case Report and Review of the Literature

Background. Hepatic angiomyolipomas are uncommon non-cancerous mesenchymal tumors that belong to the perivascular epithelioid cell tumour group. Smooth muscle cells, fat cells and blood vessels can be observed in these types of neoplasm. Case presentation. We present the case of a 50-year-old patient. The patient was referred to the National Cancer Institute after an abdominal ultrasound, which incidentally revealed a mass in the liver. A whole body computed tomography scan showed a large liver mass, in the VII/VIII/V/VI segments. Trisegmenthomy of the right liver lobe was performed. Pathological examination revealed a rare, but benign tumour – angiomyolipoma. The postoperative course was uneventful and the patient was discharged on postoperative day 9. Two months following the surgery, the patient has no recurrence or late complications. Conclusion. Hepatic angiomyolipoma is a rare, usually benign tumour with malignant potential. It is can be diagnosed by radiological tests, biopsy or after surgery. The most common treatment is surgical resection.

Ultrasound-guided procedures for the management of chronic thoracic back pain: a technical review.

Pain arising from the thoracic region has been reported to be potentially as debilitating as cervical or lumbar back pain, and may stem from a vast number of spinal sources, including zygapophysial, costovertebral and costotransverse joints, intervertebral discs, ligaments, fascia, muscles, and nerve roots. Over the last two decades, the use of ultrasound in interventional spinal procedures has been rapidly evolving, due to the ultrasound capabilities of visualizing soft tissues, including muscle layers, pleura, nerves, and blood vessels, allowing for real-time needle tracking, while also reducing radiation exposure to both patient and physician, when compared to traditional fluoroscopy guidance. However, its limitations still preclude it from being the imaging modality of choice for some thoracic spinal procedures, notably epidural (interlaminar and transforaminal approaches) and intradiscal injections. In this technical review, we provide an overview of five thoracic spinal injections that are amenable to ultrasound guidance. We start by discussing their clinical utility, followed by the relevant topographic anatomy, and then provide an illustrated technical description of each of the procedures discussed: (1) erector spinae plane block; (2) intra-articular thoracic zygapophyseal (facet) joint injection; (3) thoracic medial branch block; (4) costotransverse joint injection; and (5) costovertebral joint injection.

Two Affordable, High-Fidelity Central Venous Models for Ultrasound-Guided Interventional Training.

Ultrasound-guided vascular access is an increasingly popular technique due to its reduced complication and higher success rates. Commercially bought training phantoms allow providers to develop tactile skills in a low-risk setting, but are also expensive and poorly accessible. This study analyzes the efficacy of homemade, low-cost, gelatin-based central line vascular models to teach vascular anatomy and intravascular access techniques in training physicians. A gelatin mold was created using a mixture of unflavored gelatin, hot water, psyllium husk powder, and rubbing alcohol. Latex tubing, balloons, precooked hot dog, and tofu were inserted to simulate arteries, veins, nerves, and the sternocleidomastoid muscle, respectively. Medical students from a single institution participated in a 90-minute workshop led by interventional radiology residents. Participants completed presurveys and postsurveys that assessed knowledge acquisition and confidence levels related to acquiring central access. All images were obtained using a USB-C Butterfly iQ probe. Twenty medical students were analyzed after the workshop. There was a statistically significant increase in self-reported confidence in basic ultrasound use (adjusting gain, depth, probe manipulation), localizing major anatomical structures, using ultrasound for vessel access, and reported ease in identifying muscle, nerves, and major blood vessels under ultrasound. There was also a significant increase in correctly identified anatomical landmarks after the workshop, including the sternocleidomastoid muscle, internal jugular vein, carotid artery, femoral nerve, femoral artery, and femoral vein. Our findings suggest that our homemade, low-cost, gelatin-based models were effective in teaching vascular anatomy and ultrasound-guided vascular access techniques to training physicians.

ORAL ANGIOLEIOMYOMA: A CASE REPORT

Angioleiomyoma is a benign neoplasm of perivascular origin and uncommon in the oral cavity. This lesion is treated with surgery and prognosis is considered favorable. This paper reports the case of a 36-year-old melanoderma patient who presented to a diagnostic service reporting an increase in volume with approximately five years of evolution and without painful symptoms. Clinically, a nodular, normal-colored lesion of fibrous consistency was observed, located in the mucous of the right upper lip, measuring approximately 15 mm in its largest dimensions. In line with the clinical aspect, an excisional biopsy of the entire lesion was performed and later sent for anatomopathological analysis with a diagnostic hypothesis of salivary gland neoplasia. Histopathological examination showed proliferation of smooth muscle cells and blood vessels of different sizes with thick walls. The histological findings were compatible for the diagnosis of angioleiomyoma. Patient has been without injury for six months. Angioleiomyoma is a benign neoplasm of perivascular origin and uncommon in the oral cavity. This lesion is treated with surgery and prognosis is considered favorable. This paper reports the case of a 36-year-old melanoderma patient who presented to a diagnostic service reporting an increase in volume with approximately five years of evolution and without painful symptoms. Clinically, a nodular, normal-colored lesion of fibrous consistency was observed, located in the mucous of the right upper lip, measuring approximately 15 mm in its largest dimensions. In line with the clinical aspect, an excisional biopsy of the entire lesion was performed and later sent for anatomopathological analysis with a diagnostic hypothesis of salivary gland neoplasia. Histopathological examination showed proliferation of smooth muscle cells and blood vessels of different sizes with thick walls. The histological findings were compatible for the diagnosis of angioleiomyoma. Patient has been without injury for six months.

Vasculogenic Mesodermal Cells Derived From Induced Pluripotent Stem Cells Improve Limb Perfusion and Decrease Necrosis in Murine Models of Hindlimb Ischemia

Critical limb-threatening ischemia (CLTI) is a national health care priority as there has been a 50% increase in amputations from 2010 to 2018. Unlike other cell products that simply secrete proangiogenic growth factors, induced pluripotent stem cell (iPSC)-derived mesodermal cells have the capacity to differentiate into endothelial cells and smooth muscle cells and form functioning blood vessels in vivo. Here we discuss the effects of intramuscular injection of human iPSC mesodermal cells (VSC100) on limb perfusion and limb necrosis. iPSCs were produced using methods including Yamanaka factors (Broxmeyer et al [21393480]). The iPSC cells were differentiated using sequential Activin A, BMP4, vascular endothelial growth factor, and fibroblast growth factor 2 to promote mesodermal and endothelial cell differentiation. Murine CLTI models were created via excision of the common femoral artery in male BALB-C Nude mice, aged 6 to 8 weeks. After creation of the CLTI model mice were randomized to 1 × 106 VSC100 cells labeled with td-tomato (red fluorescence) or vehicle control injected into the gastrocnemius and gracilis muscles (n = 10/group) at 7 to 14 days postinduction of ischemia. Limb perfusion was measured with laser speckle contrast imaging up to day 64, qualitative analysis of VSC100 differentiation into capillaries was assessed with immunohistochemical staining for isolectin B4 and human CD31 and confocal microscopy to detect td-tomato. Degree of tissue loss of the index limb was quantified with established necrosis scores. VSC100-treated BALB-C nude mice showed a significant increase in limb perfusion as compared to vehicle controls with average percent blood flow/contralateral limb ratios of 45% in treated groups compared to 25% in control (P < .001) at day 64 (Fig 1). Limb necrosis scores showed similar results, in that necrosis was statistically significantly reduced in iPSC-treated vs vehicle control treated groups (Fig 2). Immunohistochemical analysis showed qualitative significant deposition of cells of interest in our CLTI models. iPSC-derived VSC100 is a novel approach to treating CTLI as the cells are capable of forming functioning blood vessels in ischemia skeletal muscle, improve tissue perfusion, and mitigate tissue necrosis. These early results and data support further translational work to support development of an investigational new drug for future clinical trial studies.Fig 2Clinical scoring ratio of chronic limb-threatening ischemia (CLTI) in control vs treated groups. Mouse population same as in Fig 1 (n = 10/group).View Large Image Figure ViewerDownload Hi-res image Download (PPT)