Source Of Mesenchymal Stem/stromal Cells Research Articles

Synovium-Derived and Bone-Derived Mesenchymal Stem/Stromal Cells from Early OA Patients Show Comparable In Vitro Properties to Those of Non-OA Patients.

Degenerative disorders like osteoarthritis (OA) might impair the ability of tissue-resident mesenchymal stem/stromal cells (MSCs) for tissue regeneration. As primary cells with MSC-like properties are exploited for patient-derived stem cell therapies, a detailed evaluation of their in vitro properties is needed. Here, we aimed to compare synovium-derived and bone-derived MSCs in early hip OA with those of patients without OA (non-OA). Tissues from three synovial sites of the hip (paralabral synovium, cotyloid fossa, inner surface of peripheral capsule) were collected along with peripheral trabecular bone from 16 patients undergoing hip arthroscopy (8 early OA and 8 non-OA patients). Primary cells isolated from tissues were compared using detailed in vitro analyses. Gene expression profiling was performed for the skeletal stem cell markers podoplanin (PDPN), CD73, CD164 and CD146 as well as for immune-related molecules to assess their immunomodulatory potential. Synovium-derived and bone-derived MSCs from early OA patients showed comparable clonogenicity, cumulative population doublings, osteogenic, adipogenic and chondrogenic potential, and immunophenotype to those of non-OA patients. High PDPN/low CD146 profile (reminiscent of skeletal stem cells) was identified mainly for non-OA MSCs, while low PDPN/high CD146 mainly defined early OA MSCs. These data suggest that MSCs from early OA patients are not affected by degenerative changes in the hip. Moreover, the synovium represents an alternative source of MSCs for patient-derived stem cell therapies, which is comparable to bone. The expression profile reminiscent of skeletal stem cells suggests the combination of low PDPN and high CD146 as potential biomarkers in early OA.

Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential.

Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied.

＜Editors' Choice＞ Mesenchymal stem/stromal cells generated from induced pluripotent stem cells are highly resistant to senescence.

The use of mesenchymal stem/stromal cells (MSCs) has attracted attention in the field of regenerative medicine based on their anti-inflammatory and tissue repair-promoting effects. Bone marrow is widely used as a source of MSCs; however, the performance of bone marrow (BM)-MSCs deteriorates as the cells age along with cell passaging. Recently, it has been reported that MSCs can be generated from induced pluripotent stem cells (iPSCs), which is expected to represent a new source of MSCs. However, few studies have investigated aging in iPSC-derived MSCs (iMSCs) and their functions. In this study, we investigated whether iMSCs overcome cellular senescence compared to that in BM-MSCs. Cellular senescence was quantitatively evaluated by staining iMSCs and BM-MSCs with fluorescein di-β-D-galactopyranoside (FDG) and following flow cytometer analysis. The hepatocyte growth factor (HGF) concentration in the culture supernatant was also measured as a factor in the therapeutic efficacy of nephritis. The iMSCs did not reach their proliferation limit and their morphology did not change even after 10 passages. The FDG positivity of BM-MSCs increased with passaging, whereas that in iMSCs did not increase. The HGF concentration increased with passaging in iMSCs. In conclusion, our results suggest that iMSCs may be less susceptible to senescence than BM-MSCs and may be used in clinical applications.

Characterization of canine adipose- and endometrium-derived Mesenchymal Stem/Stromal Cells and response to lipopolysaccharide.

Mesenchymal stem/stromal cells (MSCs) are used for regenerative therapy in companion animals. Their potential was initially attributed to multipotency, but subsequent studies in rodents, humans and veterinary species evidenced that MSCs produce factors that are key mediators of immune, anti-infective and angiogenic responses, which are essential in tissue repair. MSCs preparations have been classically obtained from bone marrow and adipose tissue (AT) in live animals, what requires the use of surgical procedures. In contrast, the uterus, which is naturally exposed to external insult and infection, can be accessed nonsurgically to obtain samples, or tissues can be taken after neutering. In this study, we explored the endometrium (EM) as an alternative source of MSCs, which we compared with AT obtained from canine paired samples. Canine AT- and EM-MSCs, formed CFUs when seeded at low density, underwent tri-lineage differentiation into adipocytes, osteocytes and chondrocytes, and expressed the CD markers CD73, CD90 and CD105, at equivalent levels. The immune genes IL8, CCL2 and CCL5 were equally expressed at basal levels by both cell types. However, in the presence of the inflammatory stimulus lipopolysaccharide (LPS), expression of IL8 was higher in EM- than in AT-MSCs (p < 0.04) while the other genes were equally elevated in both cell types (p < 0.03). This contrasted with the results for CD markers, where the expression was unaltered by exposing the MSCs to LPS. Overall, the results indicate that canine EM-MSCs could serve as an alternative cell source to AT-MSCs in therapeutic applications.

Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source.

Mesenchymal stem/stromal cells (MSCs) hold great promise for the treatment of autoimmune conditions given their immunomodulatory properties. Based on the low immunogenicity of MSCs, it is tempting to consider the expansion of MSCs from a “universal donor” in culture prior to their allogeneic applications for immediate care. This raises the critical question of the criteria we should use to select the best “universal donor”. It is also imperative we compare the “universal” approach with a “personalized” one for clinical value. In addition to the call for MHC-matching, recent studies suggest that factors including age, sex, and biological sources of MSCs can have significant impact on therapy outcome. Here, we will review findings from these studies, which shed light on the variables that can guide the important choice of “universal” or “personalized” MSC therapy for autoimmune diseases.

Lineage Differentiation Potential of Different Sources of Mesenchymal Stem Cells for Osteoarthritis Knee.

Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and secretomes to provide a better regenerative milieu in degenerative diseases. The successful regeneration of cartilage depends on the selection of the appropriate source of MSCs, the quality, quantity, and frequency of MSCs to be injected, and the selection of the patient at an appropriate stage of the disease. However, confirmation on the most favorable source of MSCs remains uncertain to clinicians. The lack of knowledge in the current cellular treatment is uncertain in terms of how beneficial MSCs are in the long-term or short-term (resolution of pain) and improved quality of life. Whether MSCs treatments have any superiority, exists due to sources of MSCs utilized in their potential to objectively regenerate the cartilage at the target area. Many questions on source and condition remain unanswered. Hence, in this review, we discuss the lineage differentiation potentials of various sources of MSCs used in the management of knee osteoarthritis and emphasize the role of tissue engineering in cartilage regeneration.

The Molecular Mechanisms Through Which Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration.

Multiple sclerosis (MS) is a debilitating degenerative disease characterized by an immunological attack on the myelin sheath leading to demyelination and axon degeneration. Mesenchymal stem/stromal cells (MSCs) and secreted extracellular vesicles (EVs) have become attractive targets as therapies to treat neurodegenerative diseases such as MS due to their potent immunomodulatory and regenerative properties. The placenta is a unique source of MSCs (PMSCs), demonstrates "fetomaternal" tolerance during pregnancy, and serves as a novel source of MSCs for the treatment of neurodegenerative diseases. PMSCs and PMSC-EVs have been shown to promote remyelination in animal models of MS, however, the molecular mechanisms by which modulation of autoimmunity and promotion of myelination occurs have not been well elucidated. The current review will address the molecular mechanisms by which PMSC-EVs can promote remyelination in MS.

Generation and characterization of human mesenchymal stem/stromal cells for cell therapy applications.

Stem Cell based-therapy is an active area of research in regenerative medicine. Mesenchymal stem/stromal cells (MSCs) are multipotent adult stem/progenitor cells, which could be easily expanded in vitro and have the ability to selectively migrate toward injured tissues, evade the immune system, and secrete trophic factors to support the repair of damaged tissues. The use of MSCs for cell and regenerative purposes has garnered the attention of scientists and clinicians. However, one of the most important issues before use MSCs in clinical practice is to standardize a number of aspects related to the source of MSCs, culture conditions, pre-condition protocols before transplantation, administration route, doses, or treatment duration. In this chapter, we described two standard protocols to isolate MSCs from bone marrow and umbilical cord connective tissue. In addition, basic characterization including immunophenotyping by flow cytometry and differentiation capability is also described.

Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials.

Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

ABSTRACT Introduction Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene- or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.

Role and application of stem cells in dental regeneration: A comprehensive overview

Recently, a growing attention has been observed toward potential advantages of stem cell (SC)-based therapies in regenerative treatments. Mesenchymal stem/stromal cells (MSCs) are now considered excellent candidates for tissue replacement therapies and tissue engineering. Autologous MSCs importantly contribute to the state-of-the-art clinical strategies for SC-based alveolar bone regeneration. The donor cells and immune cells play a prominent role in determining the clinical success of MSCs therapy. In line with the promising future that stem cell therapy has shown for tissue engineering applications, dental stem cells have also attracted the attention of the relevant researchers in recent years. The current literature review aims to survey the variety and extension of SC-application in tissue-regenerative dentistry. In this regard, the relevant English written literature was searched using keywords: “tissue engineering”, “stem cells”, “dental stem cells”, and “dentistry strategies”. According to the available database, SCs application has become increasingly widespread because of its accessibility, plasticity, and high proliferative ability. Among the growing recognized niches and tissues containing higher SCs, dental tissues are evidenced to be rich sources of MSCs. According to the literature, dental SCs are mostly present in the dental pulp, periodontal ligament, and dental follicle tissues. In this regard, the present review has described the recent findings on the potential of dental stem cells to be used in tissue regeneration.

Methodological Approaches to Development of Cell-based Medicinal Product for Treatment of Patients with Cold Injury in the Arctic

Frostbite is the most common type of traumatic injuries in the cold climate of the Arctic. Post-traumatic recovery of the patients takes a long time and often leads to the loss of the damaged limb. A promising approach for frostbite therapy could be treatment with mesenchymal stem/stromal cells (MSCs), which are widely used in regenerative medicine for different applications. Here, we aimed to discuss the possibility of frostbite treatment with MSCs. The success of MSC use for therapy of different injures depends on multiple factors including the source and functional state of MSCs. These aspects along with strategies for improvement of therapeutic effect of MSC treatment are also discussed in detail.

Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.

Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide.Current therapies totreat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials. To determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June2020), Embase (1980 to 8 June2020), and CINAHL (1982 to 8 June2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs. For each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence. Our search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studieswe excluded. There is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.

Infrapatellar Fat Pad/Synovium Complex in Early-Stage Knee Osteoarthritis: Potential New Target and Source of Therapeutic Mesenchymal Stem/Stromal Cells.

The infrapatellar fat pad (IFP) has until recently been viewed as a densely vascular and innervated intracapsular/extrasynovial tissue with biomechanical roles in the anterior compartment of the knee. Over the last decade, secondary to the proposition that the IFP and synovium function as a single unit, its recognized tight molecular crosstalk with emerging roles in the pathophysiology of joint disease, and the characterization of immune-related resident cells with varying phenotypes (e.g., pro and anti-inflammatory macrophages), this structural complex has gained increasing attention as a potential therapeutic target in patients with various knee pathologies including osteoarthritis (KOA). Furthermore, the description of the presence of mesenchymal stem/stromal cells (MSC) as perivascular cells within the IFP (IFP-MSC), exhibiting immunomodulatory, anti-fibrotic and neutralizing activities over key local mediators, has promoted the IFP as an alternative source of MSC for cell-based therapy protocols. These complementary concepts have supported the growing notion of immune and inflammatory events participating in the pathogenesis of KOA, with the IFP/synovium complex engaging not only in amplifying local pathological responses, but also as a reservoir of potential therapeutic cell-based products. Consequently, the aim of this review is to outline the latest discoveries related with the IFP/synovium complex as both an active participant during KOA initiation and progression thus emerging as a potential target, and a source of therapeutic IFP-MSCs. Finally, we discuss how these notions may help the design of novel treatments for KOA through modulation of local cellular and molecular cascades that ultimately lead to joint destruction.

Human umbilical cord derived mesenchymal stem cells induce tissue repair and regeneration in collagen-induced arthritis in rats

The current study highlights the potential use of MSCs as a cell-based therapeutic option for the treatment of inflammatory RA.

Impact of developmental origin, niche mechanics and oxygen availability on osteogenic differentiation capacity of mesenchymal stem/stromal cells.

Mesenchymal Stem/Stromal Cells (MSCs) have been widely considered as a promising source of cells for tissue regeneration. Among other stem cells, they are characterized by a high osteogenic potential. Intensive studies in this field had shown that even if basic osteogenic differentiation is relatively simple, its clinical application requires more sophisticated approaches to prepare effective and safe cell therapy products. The aim of this review is to underline biological, physical and chemical factors which play a crucial role in osteogenic differentiation of MSCs. Existence of two distinct mechanisms of ossification (intramembranous and endochondral) indicate that choosing a proper source of MSCs may be critical for successful regeneration of a particular bone type. In this context, Dental Pulp Stem Cells representing a group of MSCs and originating from neural crest ( a structure responsible for development of cranial bones) are considered as the most promising for skull bone defect repair. Factors which facilitate osteogenic differentiation of MSCs include changes in forces exerted on cells during development. Thus, culturing of cells in hydrogels or on biocompatible three-dimensional scaffolds improves osteogenic differentiation of MSCs by both, the mechanotransductive and chemical impact on cells. Moreover, atmospheric oxygen concentration routinely used for cell cultures in vitro does not correspond to lower oxygen concentration present in stem cell niches. A decrease in oxygen concentration allows to create more physiological cell culture conditions, mimicking the ones in stem cell niches, which promote the MSCs stemness. Altogether, factors discussed in this review provide exciting opportunities to boost MSCs propagation and osteogenic differentiation which is crucial for successful clinical applications.

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases.

Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The phenotype and expression of adhesion molecules (intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1) on commercially available healthy donors (HD), ASC lines (n = 5) and on ASCs isolated from patients with systemic lupus erythematosus (SLE, n = 16), systemic sclerosis (SSc, n = 17) and ankylosing spondylitis (AS, n = 16) were analyzed by flow cytometry. The secretion of immunomodulatory factors by untreated and cytokine-treated ASCs was measured by ELISA. RD/ASCs have reduced basal levels of CD90 and ICAM-1 expression, correlated with interleukin (IL)-6 and transforming growth factor (TGF)-β1 release, respectively. Compared with HD/ASCs, untreated and tumour necrosis factor (TNF) + interferon (IFN)-γ (TI)-treated RD/ASCs produced similar amounts of prostaglandin E2 (PGE2), IL-6, leukemia inhibiting factor (LIF), and TGF-β1, more IL-1Ra, soluble human leukocyte antigen G (sHLA-G) and tumor necrosis factor-inducible gene (TSG)-6, but less kynurenines and galectin-3. Basal secretion of galectin-3 was inversely correlated with the patient’s erythrocyte sedimentation rate (ESR) value. IFN-α and IL-23 slightly raised galectin-3 release from SLE/ASCs and AS/ASCs, respectively. TGF-β1 up-regulated PGE2 secretion by SSc/ASCs. In conclusion, RD/ASCs are characterized by low basal levels of CD90 and ICAM-1 expression, upregulated secretion of IL-1Ra, TSG-6 and sHLA-G, but impaired release of kynurenines and galectin-3. These abnormalities may modify biological activities of RD/ASCs.

Isolation and culture of human endometrial derived cells as an in vitro model for future implantation studies

Introduction: Monthly regeneration of endometrium after cyclical mensturation confirmed the ability of specific population of the cells that presence in the basalis layer and undergone consecutive hormonal changes that could prepared the endometrial layer for probable implantation. These cells, known as, stem cell. The aim of this study was the isolation and culture of human endometrial derived mesenchymal stem/stromal cells (EnMSCs). Methods: .In this study, human endometrial tissues were collected after fully-informed patient consent, which attended the Research and Clinical Center for Infertility. After washing and enzymatic treatment, EnMSCs were isolated and cultured in vitro. Results: Cells from endometrium were successfully isolated using enzymatically treatment and mechanically dissociation, then cultured and expanded for several passages for further characterization and evaluations. Endometrium derived cells were morphologically similar to mesenchymal stem/stromal cells (MSCs). Conclusion: The results of the present study confirm previous reports in vitro studies for the isolation and culture of human EnMSCs. Endometrial tissue is a part of uterus with available source of MSCs with self-renewal and differentiation capacity that undergoes a cyclical regeneration every month in normal women’s life span. In this regard, human EnMSCs could be used for future novel therapeutic methods in regenerative medicine for treatment of uterine-factor infertile patients, which can lead to recurrent pregnancy loss (RPL) and finally resolve of surrogacy problems.

The Immunomodulatory Potential of Wharton's Jelly Mesenchymal Stem/Stromal Cells.

The benefits attributed to mesenchymal stem/stromal cells (MSC) in cell therapy applications are mainly attributed to the secretion of factors, which exhibit immunomodulatory and anti-inflammatory effects and stimulate angiogenesis. Despite the desirable features such as high proliferation levels, multipotency, and immune response regulation, there are important variables that must be considered. Although presenting similar morphological aspects, MSC collected from different tissues can form heterogeneous cellular populations and, therefore, manifest functional differences. Thus, the source of MSC should be a factor to be considered in the development of novel therapies. The following text presents an updated review of recent research outcomes related to Wharton's jelly mesenchymal stem/stromal cells (WJ-MSC), harvested from umbilical cords and considered novel and potential candidates for the development of cell-based approaches. This text highlights information on how WJ-MSC affect immune responses in comparison with other sources of MSC.

Mesenchymal Stem/Stromal Cell-Based Therapy for Heart Failure - What Is the Best Source?

Transplantation of stem/progenitor cells is a promising, emerging treatment for heart failure (HF) in the modern era. Mesenchymal stem/stromal cells (MSCs) are considered as one of the most promising cell sources for this purpose, because of their powerful secretion of reparative factors and immunomodulatory ability. To date, various sources of MSCs have been examined for the treatment of HF in preclinical or clinical studies, including adult tissues (bone marrow and adipose tissue), perinatal tissues (umbilical cord and amnion), and pluripotent stem cells (induced pluripotent stem cells and embryonic stem cells). Adult tissue-derived MSCs have been more extensively examined. Previous clinical trials have suggested the safety and feasibility of these MSCs in HF treatment, but their therapeutic effects remain arguable. Perinatal tissue-derived MSCs have the advantages of removing the necessity of invasiveness biopsy and of mass production. An increasing number of clinical studies (albeit early stage) have been conducted. Pluripotent stem cell-derived MSCs may be another promising source because of their mass-production ability underpinned by their unlimited expansion with consistent quality. However, the risk of tumorigenicity restricts their clinical application. In this review, we summarize the current information available from preclinical and clinical studies, highlighting the advantages and disadvantages of each MSC type. This will provide an insight into consideration of the best MSC source for the treatment of HF.