scholarly journals Extracellular Matrix Enhances Therapeutic Effects of Stem Cells in Regenerative Medicine

Author(s):  
Yan Nie ◽  
Shuaiqiang Zhang ◽  
Na Liu ◽  
Zongjin Li
2014 ◽  
Vol 5 ◽  
pp. BTRI.S12331 ◽  
Author(s):  
John W. Cassidy

Modern medicine faces a growing crisis as demand for organ transplantations continues to far outstrip supply. By stimulating the body's own repair mechanisms, regenerative medicine aims to reduce demand for organs, while the closely related field of tissue engineering promises to deliver “of-the-self” organs grown from patients' own stem cells to improve supply. To deliver on these promises, we must have reliable means of generating complex tissues. Thus far, the majority of successful tissue engineering approaches have relied on macroporous scaffolds to provide cells with both mechanical support and differentiative cues. In order to engineer complex tissues, greater attention must be paid to nanoscale cues present in a cell's microenvironment. As the extracellular matrix is capable of driving complexity during development, it must be understood and reproduced in order to recapitulate complexity in engineered tissues. This review will summarize current progress in engineering complex tissue through the integration of nanocomposites and biomimetic scaffolds.


2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Ross E. B. Fitzsimmons ◽  
Matthew S. Mazurek ◽  
Agnes Soos ◽  
Craig A. Simmons

As a result of over five decades of investigation, mesenchymal stromal/stem cells (MSCs) have emerged as a versatile and frequently utilized cell source in the fields of regenerative medicine and tissue engineering. In this review, we summarize the history of MSC research from the initial discovery of their multipotency to the more recent recognition of their perivascular identity in vivo and their extraordinary capacity for immunomodulation and angiogenic signaling. As well, we discuss long-standing questions regarding their developmental origins and their capacity for differentiation toward a range of cell lineages. We also highlight important considerations and potential risks involved with their isolation, ex vivo expansion, and clinical use. Overall, this review aims to serve as an overview of the breadth of research that has demonstrated the utility of MSCs in a wide range of clinical contexts and continues to unravel the mechanisms by which these cells exert their therapeutic effects.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ilona Kalaszczynska ◽  
Katarzyna Ferdyn

Around 5 million annual births in EU and 131 million worldwide give a unique opportunity to collect lifesaving Wharton’s jelly derived mesenchymal stem cells (WJ-MSC). Evidences that these cells possess therapeutic properties are constantly accumulating. Collection of WJ-MSC is done at the time of delivery and it is easy and devoid of side effects associated with collection of adult stem cells from bone marrow or adipose tissue. Likewise, their rate of proliferation, immune privileged status, lack of ethical concerns, nontumorigenic properties make them ideal for both autologous and allogeneic use in regenerative medicine applications. This review provides an outline of the recent findings related to WJ-MSC therapeutic effects and possible advantage they possess over MSC from other sources. Results of first clinical trials conducted to treat immune disorders are highlighted.


2021 ◽  
Vol 22 (2) ◽  
pp. 763
Author(s):  
Vitale Miceli ◽  
Matteo Bulati ◽  
Gioacchin Iannolo ◽  
Giovanni Zito ◽  
Alessia Gallo ◽  
...  

Mesenchymal stromal/stem cells (MSCs) are multipotent adult stem cells that support homeostasis during tissue regeneration. In the last decade, cell therapies based on the use of MSCs have emerged as a promising strategy in the field of regenerative medicine. Although these cells possess robust therapeutic properties that can be applied in the treatment of different diseases, variables in preclinical and clinical trials lead to inconsistent outcomes. MSC therapeutic effects result from the secretion of bioactive molecules affected by either local microenvironment or MSC culture conditions. Hence, MSC paracrine action is currently being explored in several clinical settings either using a conditioned medium (CM) or MSC-derived exosomes (EXOs), where these products modulate tissue responses in different types of injuries. In this scenario, MSC paracrine mechanisms provide a promising framework for enhancing MSC therapeutic benefits, where the composition of secretome can be modulated by priming of the MSCs. In this review, we examine the literature on the priming of MSCs as a tool to enhance their therapeutic properties applicable to the main processes involved in tissue regeneration, including the reduction of fibrosis, the immunomodulation, the stimulation of angiogenesis, and the stimulation of resident progenitor cells, thereby providing new insights for the therapeutic use of MSCs-derived products.


Author(s):  
Tomomi Sato ◽  
Takumi Ito ◽  
Hiroshi Handa

Thalidomide, a sedative drug that was once excluded from the market owing to its teratogenic properties, was later found to be effective in treating multiple myeloma. We had previously demonstrated that cereblon (CRBN) is the target of thalidomide embryopathy and acts as a substrate receptor for the E3 ubiquitin ligase complex, Cullin-Ring ligase 4 (CRL4CRBN) in zebrafish and chicks. CRBN was originally identified as a gene responsible for mild intellectual disability in humans. Fetuses exposed to thalidomide in early pregnancy were at risk of neurodevelopmental disorders such as autism, suggesting that CRBN is involved in prenatal brain development. Recently, we found that CRBN controls the proliferation of neural stem cells in the developing zebrafish brain, leading to changes in brain size. Our findings imply that CRBN is involved in neural stem cell growth in humans. Accumulating evidence shows that CRBN is essential not only for the teratogenic effects but also for the therapeutic effects of thalidomide. This review summarizes recent progress in thalidomide and CRBN research, focusing on the teratogenic and therapeutic effects. Investigation of the molecular mechanisms underlying the therapeutic effects of thalidomide and its derivatives, CRBN E3 ligase modulators (CELMoDs), reveals that these modulators provide CRBN the ability to recognize neosubstrates depending on their structure. Understanding the therapeutic effects leads to the development of a novel technology called CRBN-based proteolysis-targeting chimeras (PROTACs) for target protein knockdown. These studies raise the possibility that CRBN-based small-molecule compounds regulating the proliferation of neural stem cells may be developed for application in regenerative medicine.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lijun Chen ◽  
Jingjing Qu ◽  
Quanhui Mei ◽  
Xin Chen ◽  
Yangxin Fang ◽  
...  

AbstractMenstrual blood-derived mesenchymal stem cells (MenSCs) have great potential in regenerative medicine. MenSC has received increasing attention owing to its impressive therapeutic effects in both preclinical and clinical trials. However, the study of MenSC-derived small extracellular vesicles (EVs) is still in its initial stages, in contrast to some common MSC sources (e.g., bone marrow, umbilical cord, and adipose tissue). We describe the basic characteristics and biological functions of MenSC-derived small EVs. We also demonstrate the therapeutic potential of small EVs in fulminant hepatic failure, myocardial infarction, pulmonary fibrosis, prostate cancer, cutaneous wound, type-1 diabetes mellitus, aged fertility, and potential diseases. Subsequently, novel hotspots with respect to MenSC EV-based therapy are proposed to overcome current challenges. While complexities regarding the therapeutic potential of MenSC EVs continue to be unraveled, advances are rapidly emerging in both basic science and clinical medicine. MenSC EV-based treatment has great potential for treating a series of diseases as a novel therapeutic strategy in regenerative medicine.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Takashi Hoshiba ◽  
Guoping Chen ◽  
Chiho Endo ◽  
Hiroka Maruyama ◽  
Miyuki Wakui ◽  
...  

Stem cells are a promising cell source for regenerative medicine. Stem cell differentiation must be regulated for applications in regenerative medicine. Stem cells are surrounded by extracellular matrix (ECM)in vivo. The ECM is composed of many types of proteins and glycosaminoglycans that assemble into a complex structure. The assembly of ECM molecules influences stem cell differentiation through orchestrated intracellular signaling activated by many ECM molecules. Therefore, it is important to understand the comprehensive role of the ECM in stem cell differentiation as well as the functions of the individual ECM molecules. Decellularized ECM is a usefulin vitromodel for studying the comprehensive roles of ECM because it retains a native-like structure and composition. Decellularized ECM can be obtained fromin vivotissue ECM or ECM fabricated by cells culturedin vitro. It is important to select the correct decellularized ECM because each type has different properties. In this review, tissue-derived and cell-derived decellularized ECMs are compared asin vitroECM models to examine the comprehensive roles of the ECM in stem cell differentiation. We also summarize recent studies using decellularized ECM to determine the comprehensive roles of the ECM in stem cell differentiation.


2003 ◽  
Vol 774 ◽  
Author(s):  
A. Hari Reddi

AbstractRegenerative medicine is the science of design and manufacture of parts for functional restoration of damaged tissues due to cancer, disease and trauma. Morphogenesis is the developmental cascade of pattern formation, body plan establishment and differentiation of tissues culminating in adult form. Regeneration in general, recapitulates in parts, embryonic morphogenesis. Thus, the principles of morphogenesis can be applied to tissue engineering for regenerative medicine and surgery. The threekey ingredients for tissue engineering and regenerative medicine are inductive morphogens, responding stem cells, and extracellular matrix materials. Therefore bioactive morphogens can be integrated into materials for functional restoration by tissue engineering. A morphogen is a morphogenetic protein signal that acts on responding stem cells. Bone morphogenesis is induced by bone morphogenetic proteins (BMPs). BMPs play a role in pattern formation, cell differentiation, maintenance and regeneration of tissues. BMPs are pleiotropic and act on chemotaxis, mitosis and differentiation of progenitor stem cells. There are nearly twenty BMPs in the human genome. BMPs have actions beyond bone in development of teeth, heart, kidney, eye, skin, and brain. Thus, BMPs may be called body morphogenetic proteins. Stem cells are primordial cells with unlimited replicative potential and can be programmed by morphogens such as BMPs. Extracellular matrix is the native scaffolding material that can be used to deliver morphogens such as BMPs for tissue engineering of bone. Biomimetic materials are typically synthetic, polymeric structures that mimic extracellular matrix scaffolding by presenting the cellular binding sites found within collagens, fibronectin, proteoglycans and glycoproteins. Materials that mimic extracellular matrix scaffolding such as BMPs bind to collagens I&IV, heparan sulfate and heparin. BMPs bound to collagen acts as a composite biomaterial to initiate bone formation and the shape can be molded by an appropriate template. In addition to including BMPs in a carrier matrix, the geometry of the carrier matrix is critical for optimal tissue engineering. For example: collagen particles smaller than 44μm are feeble in bone induction compared to the coarse (420μm) particles. Gene therapy approaches using genes for morphogenesis such as BMPs allows a sustained, prolonged secretion of gene products. Thus, morphogens integrated into biomaterials may be useful in regenerative medicine.


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