scholarly journals Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Chi Zhang ◽  
Wei Zhang ◽  
Dashuai Zhu ◽  
Zhenhua Li ◽  
Zhenzhen Wang ◽  
...  

Abstract Background Osteoporosis is a chronic condition affecting patients’ morbidity and mortality and represents a big socioeconomic burden. Because stem cells can proliferate and differentiate into bone-forming cells, stem cell therapy for osteoporosis has been widely studied. However, cells as a live drug face multiple challenges because of their instability during preservation and transportation. In addition, cell therapy has potential adverse effects such as embolism, tumorigenicity, and immunogenicity. Results Herein, we sought to use cell-mimicking and targeted therapeutic nanoparticles to replace stem cells. We fabricated nanoparticles (NPs) using polylactic-co-glycolic acid (PLGA) loaded with the secretome (Sec) from mesenchymal stem cells (MSCs) to form MSC-Sec NPs. Furthermore, we cloaked the nanoparticles with the membranes from C–X–C chemokine receptor type 4 (CXCR4)-expressing human microvascular endothelial cells (HMECs) to generate MSC-Sec/CXCR4 NP. CXCR4 can target the nanoparticles to the bone microenvironment under osteoporosis based on the CXCR4/SDF-1 axis. Conclusions In a rat model of osteoporosis, MSC-Sec/CXCR4 NP were found to accumulate in bone, and such treatment inhibited osteoclast differentiation while promoting osteogenic proliferation. In addition, our results showed that MSC-Sec/CXCR4 NPs reduce OVX-induced bone mass attenuation in OVX rats. Graphical Abstract

2009 ◽  
Vol 35 (2) ◽  
pp. 85-93 ◽  
Author(s):  
L. Vija ◽  
D. Farge ◽  
J.-F. Gautier ◽  
P. Vexiau ◽  
C. Dumitrache ◽  
...  

2014 ◽  
Vol 20 ◽  
pp. S128-S131 ◽  
Author(s):  
Hideki Mochizuki ◽  
Chi-Jing Choong ◽  
Toru Yasuda

2021 ◽  
Author(s):  
Lianxu Cui ◽  
Yasmeen Saeed ◽  
Haomin Li ◽  
Jingli Yang

Traumatic brain injury (TBI) is a serious health concern, yet there is a lack of standardized treatment to combat its long-lasting effects. The objective of the present study was to provide an overview of the limitation of conventional stem cell therapy in the treatment of TBI and to discuss the application of novel acellular therapies and their advanced strategies to enhance the efficacy of stem cells derived therapies in the light of published study data. Moreover, we also discussed the factor to optimize the therapeutic efficiency of stem cell-derived acellular therapy by overcoming the challenges for its clinical translation. Hence, we concluded that acellular therapy possesses the potential to bring a breakthrough in the field of regenerative medicine to treat TBI.


2020 ◽  
Vol 22 (3) ◽  
pp. 286-305 ◽  
Author(s):  
Shuai Zhang ◽  
Brittany Bolduc Lachance ◽  
Bilal Moiz ◽  
Xiaofeng Jia

Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and in vivo potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.


2011 ◽  
Vol 10 (2) ◽  
pp. 122-128 ◽  
Author(s):  
N. S. Zhukova ◽  
I. I. Staroverov

Heart failure (HF) is one of the leading death causes in patients with myocardial infarction (MI). The modern methods of reperfusion MI therapy, such as thrombolysis, surgery and balloon revascularization, even when performed early, could fail to prevent the development of large myocardial damage zones, followed by HF. Therefore, the researches have been searching for the methods which improve functional status of damaged myocardium. This review is focused on stem cell therapy, a method aimed at cardiac function restoration. The results of experimental and clinical studies on stem cell therapy in coronary heart disease are presented. Various types of stem cells, used for cellular cardiomyoplasty, are characterised. The methods of cell transplantation into myocardium and potential adverse effects of stem cell therapy are discussed.


2011 ◽  
Vol 300 (5) ◽  
pp. G684-G696 ◽  
Author(s):  
R. C. Mifflin ◽  
I. V. Pinchuk ◽  
J. I. Saada ◽  
D. W. Powell

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).


Author(s):  
Fariha Khaliq

Stem cell therapy is an approach to use cells that have the ability of self-renewal and to differentiate into different types of functional cells that are obtained from embryo and other postnatal sources to treat multiple disorders. These cells can be differentiated into different types of stem cells based on their specific characteristics to be totipotent, unipotent, multipotent or pluripotent. As potential therapy, pluripotent stem cells are considered to be the most interesting as they can be differentiated into different type of cells with similar characteristics as embryonic stem cells. Induced pluripotent stem cells (iPSCs) are adult cells that are reprogrammed genetically into stem cells from human fibroblasts through expressing genes and transcription factors at different time intervals. In this review, we will discuss the applications of stem cell therapy using iPSCs technology in treating neurodegenerative disorder such that Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). We have also broadly highlighted the significance of pluripotent stem cells in stem cell therapy.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jinho Lee ◽  
Kyu-Yong Lee ◽  
Young-Seo Kim ◽  
Hyun Young Kim ◽  
Hyuk Sung Kwon ◽  
...  

Introduction: Stem cell therapy (SCT) has been proposed for the treatment of neurological disorders. Although there isinsufficient clinical evidence to support its efficacy, unproven SCTs are being performed worldwide. Hypothesis: In this study, we investigated the perspectives and expectations of chronic ischemic stroke patients and physicians about SCTs. Methods: A total of 250 chronic ischemic stroke patients were interviewed at 4 hospitals. Structured open and closed questions about SCT for chronic stroke were asked by trained interviewers using the conventional in-person method. In addition, 250 stroke-related physicians were randomly interviewed via an e-mail questionnaire. Results: Of the 250 patients (mean 63 years, 70% male), 121 (46%) responded that they wanted to receive SCT in spite of its unknown side effects. Around 60% of the patients anticipated physical, emotional, and psychological improvement after SCT, and 158 (63%) believed that SCT might prevent strokes. However, physicians had much lower expectations about the effectiveness of SCTs, which was not in line with patient expectations. Multivariate analysis revealed that male gender (OR: 2.00, 95% CI: 1.10-3.64), longer disease duration (OR: 1.01, 95% CI:1.00-1.02), higher modified Rankin Scale score (OR: 1.30, 95% CI 1.06-1.60), and familiarity with stem cells (OR: 1.86, 95% CI: 1.10-3.15) were independently associated with wanting SCT. The major source of information about SCT was television (68%), and the most reliable source was physicians (49%). Conclusion: Patients have unfounded expectations that SCT will improve their functioning. Considering our finding that the major source of information on stem cells is media channels but not the physician, to decrease patients’ inappropriate exposure, doctors should make more effort to educate patients using mass media with accurate information.


2016 ◽  
Vol 53 (1) ◽  
pp. 135

New research reveals combined cell therapy enhances cardiac performance following heart attack. A study by Dr. Joshua Hare, Director of Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami Miller School of Medicine finds that combination stem cell therapy, using ckit+ cardiac stem cells (CSCs) and mesenchymal stem cells (MSCs) can significantly enhance cardiac performance in chronic ischemic cardiomyopathy following a heart attack. The study centered on large animals three months after experiencing a heart attack. The animals were divided into three cohorts. The first group received transendocardial injections of MSCs, while the second group received a combination of MSCs and cardiacderived CSCs. The third group acted as a controlled placebo group. Cardiac MRIs were performed to determine cardiac function before and after therapy. Both groups of cell-treated animals exhibited a significant reduction in scar size. However, the group that received the combination of MSCs and cardiacderived CSCs also demonstrated increased viable tissue, improved contractile performance and increased formation of new cardiomyocytes, which contribute to heart repair. The group that received the combination cell therapy continued to show substantial cardiac enhancement for at least three months post treatment. While further testing is needed, these findings establish the safety and efficacy of combination cell-based treatments, taking the next steps in developing stem cell-based therapies for the prevention and treatment of cardiovascular disease in humans.


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