Case Report - Stem Cell Research and Regenerative Medicine (2023) Volume 6, Issue 2

Elevated Central Vascular Cord Stem Cells in Teenagers with Accidental Stroke

Afzaal Khan*

Afzaal Khan

*Corresponding Author:
Afzaal Khan
Afzaal Khan

Received: 01-Apr-2023, Manuscript No. srrm-23-97065; Editor assigned: 04-Apr-2023, Pre-QC No. srrm-23- 97065 (PQ); Reviewed: 18-Apr-2023, QC No. srrm-23-97065; Revised: 22- Apr-2023, Manuscript No. srrm-23- 97065 (R); Published: 28-Apr-2023, DOI: 10.37532/srrm.2023.6(2).46-49


Stem cells insufficiency, also known as peripheral arterial disease (PAD), is a condition in which there is a reduced blood flow to the limbs, usually the legs. This condition is caused by the narrowing or blockage of the arteries that supply blood to the limbs, typically due to the buildup of plaque in the arteries. The reduced blood flow can result in pain, numbness, and muscle weakness in the affected limb. Symptoms of Stem cells insufficiency may include pain in the legs while walking or climbing stairs, numbness or tingling in the legs or feet, a feeling of coldness in the lower leg or foot, and sores on the toes or feet that don’t heal. In some cases, the condition may be asymptomatic, which means that there are no noticeable symptoms.


Limb • blood • chronic • PAD


Accidental stroke is a rare cerebrovascular disease characterized by progressive stenotic occlusive lesions of the terminal segment of the internal carotid artery (ICA) and associated development of compensatory, unstable collateral vessels called moyamoya vessels [1]. These vascular features cause recurrent episodic and hemorrhagic strokes, leading to neurological morbidity and even mortality in affected patients, often young adults and children. MMA is common in East Asian countries but rarely reported in Caucasians. The first peak appears in the child from the time he is 5 years old to when he is 9 years old, and the second peak appears from the time he is 45 years old to when he is 49 years old [2]. The etiology and etiology of MMA are still unknown, but its association with a genetic disorder, high familial prevalence, and strong linkage to gene variants encoding ring finger protein 213 (RNF213)/mysterin in East Asian patients etiology of MMA. In addition, there are several reports implicating RNF213 as a sensor for mitochondrial dysfunction, hypoxia, and inflammation, and has recently been implicated in antibacterial activity and lipid metabolism. A new and important role of genetic background has not yet been outlined, but has been confirmed by a large number of pediatric cases [3].

MMA may be associated with acquired infectious diseases through abnormalities in angiogenesis and angiogenic signaling pathways [4]. It is a complex mechanism by which, inflammatory, and hydrodynamic conditions can cause disease in genetically susceptible individuals. This is strongly believed to be due to the following reasons. Strikingly, the stenotic changes observed in MMA are not characterized by lipid accumulation, inflammatory cells, or macrophage infiltration into the subintimal layer typical of atherosclerosis. Furthermore, due to the progressive narrowing of the lumen in atherosclerosis, outward vascular remodeling occurs, leading to an increase in outer diameter, in contrast to the decrease in outer diameter that occurs in MMA [5]. Pediatric MMA patients with headaches and certain symptoms can be misdiagnosed. When a child fails to accurately report their symptoms, timely diagnosis is difficult and the stroke is more likely to be completed. Common childhood behaviors such as hyperventilating and crying can cause strokes and her TIA. A fully dilated cortical vasculature contracts during chronic ischemia in response to a decrease in carbon dioxide partial pressure due to prolonged hyperventilation, ultimately leading to decreased cerebral perfusion. However, the pathophysiology of MMA in children is still not fully understood, and few studies on the pediatric population with MMA have been reported. This is due to ethical concerns and the small sample size due to the rarity of the disease. Nevertheless, MMA accounts for one-fifth of identifiable cerebral artery lesions in childhood stroke and is also known to be the leading cause of cerebrovascular disease in children in East Asia. In contrast to adults with MMA, who experience both intracranial hemorrhage and accidental stroke, pediatric MMA patients mainly suffer from transient accidental attacks (TIA) or accidental arterial stroke [6]. Stroke is a leading cause of severe long-term disability and death worldwide, but childhood stroke is a rare condition. A recent study defined MMA as the third most common underlying etiology of childhood stroke, accounting for 14% of all cases. Lee and his colleagues reported 8% of arterial strokes in children with MMA. Drug therapy remains unable to halt the progression of arterial disease, and revascularization remains the most effective treatment for pediatric MMA. Due to the current lack of knowledge about pathophysiology, several studies have demonstrated different types of biomarkers (proteins, circulating cells, etc.) in different biological matrices (peripheral blood, CSF, plasma, urine, etc. and the ultimate goal is to uncover them [7].

Recently, altered levels of circulating endothelial progenitor cells (cEPCs) were identified in body fluids of pediatric MMA patients. EPCs play important roles in physiological and pathological angiogenesis. Notably, a marked reduction in cEPCs was evident in a homogenous cohort of nonsurgical Caucasian adult MMA patients. However, little is known about their role in early disease onset. Despite conflicting data regulating her EPC numbers in children with MMA, there is consensus about the defective function observed both in vitro and in vivo. Altered levels of EPCs, cytokines, chemokines and growth factors have been detected in the body fluids of MMA patients, suggesting angiogenesis and impaired angiogenesis as possible disease mechanisms [8]. Because vascular endothelial growth factor-A (VEGF-A) plays a central role in angiogenesis and the angiogenesis of new blood vessels, regulation of VEGF-A may affect the action of angiogenic stimuli in damaged brain regions of MMA patients. The VEGF signaling pathway overlaps with many other signaling pathways, including B. angiopoietin/Thailand.

The secreted glycoprotein angiopoietin 2 (ANG-2) is a pro-angiogenic factor involved in new blood vessel formation, but also promotes pathological angiogenesis, vascular permeability, and inflammation. Indeed, ANG-2 is overexpressed in several inflammatory diseases and is involved in both direct regulation of inflammation-associated signaling pathways and inflammatory cell recruitment. Thus, upregulation of ANG- 2, which is already expressed in ECs as a vasodilator cytokine, increases angiogenesis but may cause defects in angiogenesis and a long-term general inflammatory state. Interestingly, autocrine release of ANG-2 mediates cerebral vascular collapse in MMA, and elevated serum ANG-2 levels contribute to pathologic aberrant angiogenesis and/or instability of vascular structure and function. It can cause cerebral hemorrhage in adult MMA patients. Matrix metalloproteinase 9 (MMP-9) plays a key role in the regulation of extracellular matrix remodeling and angiogenesis and is a key enzyme in the degradation of extracellular matrix proteins. Already described as a key component of MMA [9]. Interleukin-6 (IL-6) is a soluble mediator with pleiotropic effects on inflammation, immune response, and hematopoiesis. IL-6 also provides warning signals of tissue damage. Previous studies have examined IL-6 expression in MMA [10].


This study seeks to fill a gap in current knowledge about the pathophysiology of MMA by identifying comprehensive molecular and cellular profiles of plasma and CSF in children with MMA. The ultimate goal is to define putative, non-invasive new biomarkers that can be used to elucidate disease etiology and serve as potential therapeutic targets from a translational perspective. The mean age of the 16 European pediatric patients enrolled in the GEN-O-MA project he was 9.2 years (range 3–16 years). As expected, none of the patients was characterized by hemorrhagic stroke, but the majority of patients who presented with episodic events such as episodic strokes or transient episodic seizures had other there were also clinical features common in children with MMA. The entire patient cohort studied was Suzuki grade III and IV, indicating severity of the ICA or moyamoya vascular network, or progressive narrowing of collateral vessels from the ECA (external carotid artery). All patients presented with symptoms of unintended cerebrovascular events. No child in our series was diagnosed with early or late neuroradiological disease (I-II or V-VI). In most cases at our institution, the diagnosis of symptomatic MMA in the pediatric population leads to early surgical management that explains some specific findings in our current patient cohort. It presented with a steno-occlusive lesion involving both hemispheres, leading to a firm diagnosis of MMA. No prevalence was found in the proportion of boys and girls in pediatric MMA patients. This finding differed from the adult MMA cohort, which was characterized by female-favorable prevalence and previous well-established data from the literature. Such issues could be explained by the release of hormones associated with secondary sex characteristics and may provide clues to study other pathways that may be involved in this obscure disease. The incidence of MMA exhibits a bimodal age distribution. The second peak (ages 45-49) coincides with the age range of physiological menopause in Western countries, and sex hormones may play a special role. However, the specific impact of sex characteristics in MMA, especially in pediatric patients, is not fully understood. The importance of gender differences in MMA has also been reported in transcriptome profiling of her ICA in an adult patient. In this study, RNA sequencing analysis (RNAseq) identified 133 and 439 sexspecifically expressed genes (DEGs) in males and females. Another of his RNAseq studies identified a total of 533 DEGs in the peripheral blood of MMA patients, further highlighting the importance of the transcriptomic approach in multifactorial disease.

Considerable evidence in the literature supports the involvement of cEPCs in the pathogenesis and development of MMA. However, little is known about their role in early disease onset. By examining the role of cEPCs in a pediatric MMA cohort, the present study demonstrated elevated levels of circulating CD45dimCD34+CD133+ mononuclear cells in patients’ peripheral blood. The reported elevated levels may be associated with higher cEPC recruitment rates, possibly due to the presence of stenotic lesions leading to the formation of specific networks of collateral vessels. Sprouting and new vessel formation may have required the recruitment of cEPCs that migrated from the bone marrow to brain regions. No statistically significant difference was found in cEPC between the two subgroups of MMA patients (before and after neurosurgery), suggesting that neurosurgery did not affect the percentage of cEPC. Notably, a marked reduction in cEPCs was evident in a homogenous cohort of non-surgical Caucasian adult MMA patients. Other groups have suggested that cEPC is reduced in pediatric MMA patients, but the age difference between the groups analyzed may represent an underlying bias in these results. In particular, the observed control group had a mean age of 23 years, which was characterized by an older group compared to the MMA group with a mean age of 7.5 years. Age therefore appears to be an important factor in the assessment of cEPCs and in certain methodological approaches to identify and quantify cEPCs. Other circulating vascular progenitor cells are also involved in MMA. As previously reported, fibrocyte hyperplasia and proliferation suggested the involvement of smooth muscle cells. A marked increase in circulating CD34+ cells associated with angiogenesis after accidental stress has been observed in MMA patients. Similarly, elevated levels of circulating CD34+CXCR4+ cells have been found in the peripheral blood of MMA patients.


Pediatric MMA patients displayed several characteristic cellular and molecular features in both blood and CSF compared with ageand sex-matched controls. Furthermore, we highlighted differences in cEPC between pediatric and adult patients with MMA. Despite a limited patient cohort, our results are conclusive in identifying predictive and prognostic circulating biomarkers and potential therapeutic targets for personalized care in pediatric MMA patients. Support goals. It may suggest some areas of investigation that need to be confirmed by more comprehensive and prospective studies.


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