• Biohybrid
• Bioinspired
• Cancer
• Exosomes
• Hybrid nanoparticles
• Polymeric nanoparticles

• Humans
• Neoplasms/drug therapy
• Neoplasms/therapy
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Drug Carriers/chemistry
• Animals
• Nanoparticles/chemistry
• Drug Delivery Systems

• Cancer
• Cell-based therapies
• Exosomes
• Immunomodulation
• Mesenchymal stem cells

• Mesenchymal Stem Cells
• Neoplasms/therapy
• Cell Differentiation
• Humans
• Animals
• Clinical Trials as Topic

• EMT
• MCF 10A
• MCF7
• MDA231
• adhesion
• decidua basalis MSCs
• invasion
• migration
• placenta
• proliferation

• Humans
• Epithelial-Mesenchymal Transition/genetics
• Female
• Breast Neoplasms/pathology
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Mesenchymal Stem Cells/metabolism
• Placenta/metabolism
• Pregnancy
• Phenotype
• MCF-7 Cells
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Apoptosis
• Coculture Techniques
• Gene Expression Regulation, Neoplastic

• RC20/346/R King Abdullah International Medical Research Center

• Corneal tissue regeneration
• Wharton’s jelly derived mesenchymal stem cells (WJMSCs)
• hydrogel scaffold
• limbal epithelial stem cells (LESCs)
• plasma rich in growth factors (PRGF)

• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Cell Differentiation/drug effects
• Humans
• Cell Proliferation/drug effects
• Tissue Scaffolds/chemistry
• Wharton Jelly/cytology
• Hydrogels/chemistry
• Hydrogels/pharmacology
• Platelet-Derived Growth Factor/pharmacology
• Fibroins/chemistry
• Fibroins/pharmacology
• Cells, Cultured

• Anti-tumoral activity
• Co-culture
• Hyperthermia
• Mesenchymal stem cells
• Tonsillary

• Humans
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Coculture Techniques
• Palatine Tonsil/cytology
• Palatine Tonsil/metabolism
• Cell Proliferation
• Apoptosis
• Hematologic Neoplasms/therapy
• Hematologic Neoplasms/pathology
• Hyperthermia/metabolism
• Cell Line, Tumor
• K562 Cells
• Cell Survival
• Paracrine Communication

• Cancer
• Mesenchymal stem cells
• Microvesicles
• Multiple myeloma
• U266

• Humans
• Multiple Myeloma/pathology
• Multiple Myeloma/metabolism
• Apoptosis
• Mesenchymal Stem Cells/metabolism
• Cell Line, Tumor
• Cell-Derived Microparticles/metabolism
• Cell Survival
• DNA Damage

• Apoptosis
• CD34+ leukemic stem cells
• Cytokines
• Mesenchymal stem cells
• Signaling pathway

• Cell death
• Mesenchymal stem cells
• Priming
• TLR3
• TLR4
• miRSeq

• A549
• Apoptosis
• Bee venom
• Mesenchymal stem cells
• Western blot

• Humans
• Carcinoma, Non-Small-Cell Lung/metabolism
• Cisplatin/pharmacology
• Cisplatin/metabolism
• Lung Neoplasms/metabolism
• Bee Venoms/pharmacology
• Bee Venoms/metabolism
• Apoptosis
• Proto-Oncogene Proteins c-bcl-2/metabolism
• Mesenchymal Stem Cells/metabolism

• 21112006 Selçuk University Scientific Research Projects Coordination Office
• 222S178 The Scientific and Technological Research Council of Türkiye (TUBITAK) 1002 Short Term R&D Funding Program

• HMECs
• MDA231
• adhesion
• chorionic villus MSCs
• conditioned media
• epithelial to mesenchymal transition (EMT)
• flow cytometry
• invasion
• migration
• proliferation

• RC20/346 King Abdullah International Medical Research Center

Human Wharton’s jelly-derived mesenchymal stromal/stem cells (hWJ-MSCs) have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them. Recently, we reported that hWJ-MSCs and their conditioned medium have significant therapeutic radioprotective potential. This finding raised an obvious question to identify unique features of hWJ-MSCs over other sources of stem cells for a better understanding of its radioprotective mechanism.

To understand the radioprotective mechanism of soluble factors secreted by hWJ-MSCs and identification of their unique genes.

Propidium iodide staining, endogenous spleen colony-forming assay, and survival study were carried out for radioprotection studies. Homeostasis-driven proliferation assay was performed for in vivo lymphocyte proliferation. Analysis of RNAseq data was performed to find the unique genes of WJ-MSCs by comparing them with bone marrow mesenchymal stem cells, embryonic stem cells, and human fibroblasts. Gene enrichment analysis and protein-protein interaction network were used for pathway analysis.

Co-culture of irradiated murine splenic lymphocytes with WJ-MSCs offered significant radioprotection to lymphocytes. WJ-MSC transplantation increased the homeostasis-driven proliferation of the lymphocytes. Neutralization of WJ-MSC conditioned medium with granulocyte-colony stimulating factor antibody abolished therapeutic radioprotection. Transcriptome analysis showed that WJ-MSCs share several common genes with bone marrow MSCs and embryonic stem cells and express high levels of unique genes such as interleukin (IL)1-α, IL1-β, IL-6, CXCL3, CXCL5, CXCL8, CXCL2, CCL2, FLT-1, and IL-33. It was also observed that WJ-MSCs preferentially modulate several cellular pathways and processes that handle the repair and regeneration of damaged tissues compared to stem cells from other sources. Cytokine-based network analysis showed that most of the radiosensitive tissues have a more complex network for the elevated cytokines.

Systemic infusion of WJ-MSC conditioned media will have significant potential for treating accidental radiation exposed victims.

• Radioprotection
• Mesenchymal stem cells
• Wharton’s jelly-derived mesenchymal stromal/stem cells
• Cytokines
• Granulocyte-colony stimulating factor
• Network biology

• MDA231
• adhesion
• angiogenesis
• conditioned medium
• decidua parietalis MSCs
• invasion
• migration
• placenta
• proliferation

Mesenchymal stem cells (MSCs) as undifferentiated cells are specially considered in cell-based cancer therapy due to unique features such as multi-potency, pluripotency, and self-renewal. A multitude of cytokines secreted from MSCs are known to give such multifunctional attributes, but details of their role are yet to be unknown. In the present study, MSCs were cultured, characterized and co-cultured with Molt-4 cells as acute lymphoblastic leukemia cell line in a trans-well plate. Then, cultured Molt-4 alone and Molt-4 co-cultured with MSCs (10:1) were collected on day 7 and subjected to real time-PCR and Western blotting for gene and protein expression assessment, respectively. Ki-67/caspase-3 as well as telomere length were investigated by flow cytometry and real time-PCR, respectively. The results showed that MSCs caused significant decrease in telomere length as well as hTERT gene expression of Molt-4 cells. Also, gene and protein expression of BAD and P53 were significantly increased. Furthermore, the flow cytometry analysis indicated the decrease and increase of the Ki-67 and caspaspase-3 expression, respectively. It was concluded that MSCs co-cultured with Molt-4 cells could be involved in the promotion of Molt-4 cell apoptosis via caspase-3, BAD, and P53 expression. In addition, the decrease of telomere length is another effect of MSCs on Molt-4 leukemic cells.

• BAD
• Mesenchymal stem cells
• P53
• apoptotic pathway
• caspase-3
• hTERT
• telomere length

• Cancer treatment
• Cell therapy
• Gene therapy
• Regenerative medicine
• Tissue engineering

• Cell based-therapy
• Clinical agent
• Granulocyte differentiation
• Mesenchymal stem cells
• Mononuclear cells
• Protein expression.

• Angiogenic factors
• Decidual stromal cells
• Decidualization
• Mesenchymal stem/stromal cells
• Pericytes
• Pregnancy

Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy because of their high immunomodulation ability, tropism towards inflamed and injured tissues, and their easy access and isolation. Currently, there are more than 1200 registered MSC clinical trials globally. However, a lack of standardized methods to characterize cell safety, efficacy, and biodistribution dramatically hinders the progress of MSC utility in clinical practice. In this review, we summarize the current state of MSC-based cell therapy, focusing on the systemic safety and biodistribution of MSCs. MSC-associated risks of tumor initiation and promotion and the underlying mechanisms of these risks are discussed. In addition, MSC biodistribution methodology and the pharmacokinetics and pharmacodynamics of cell therapies are addressed. Better understanding of the systemic safety and biodistribution of MSCs will facilitate future clinical applications of precision medicine using stem cells.

• Cell therapy
• Mesenchymal stem/stromal cell
• Single cell imaging
• Systemic safety
• biodistribution

Background: Mesenchymal stem cells (MSCs) are an appealing source of adult stem cells for cell therapy due to the high rate of proliferation, self-renewal capability, and applicable therapy. Wharton’s jelly (WJ), the main component of the umbilical cord extracellular matrix, comprises multipotent stem cells with a high proliferation rate and self-renewal capability and has anti-cancer properties. MSCs have been reported to secrete a variety of cytokines that have a cytotoxic effect in various cancers. Oxygen tension affects MSCs proliferation, cytokines level but no in surface markers expression, MSCs’ differentiation.

We explored the cytotoxic effect and inducing apoptosis of Wharton’s jelly derived mesenchymal stem cells (WJMSCs) secretions from normoxic WJMSCs (WJMSCs-norCM) (CM: conditioned medium) and hypoxic WJMSCs (WJMSCs-hypoCM) in breast cancer cell lines (T47D and MCF7).

Materials and Methods: Cytotoxic activity was determined using the MTS assay. RT-PCR was performed to measure the expression of apoptosis-inducing genes, specifically P53, BAX, and CASP9, and the antiapoptotic gene BCL-2.

Results: WJMSCs-norCM and WJMSCs-hypoCM were potent inhibitors of the proliferation in both cell lines. WJMSCs-norCM had more anticancer activity in T47D and MCF7. The IC₅₀ value of WJMSCs-norCM on MCF7 was 42.34%, and on T47D was 42.36%. WJMSCs-norCM significantly induced the gene expression of apoptotic P53, BAX, and CASP9 and insignificantly decreased the antiapoptotic gene BCL-2 in both MCF7 and T47D cells. WJMSCs-CM has anticancer activity by inducing P53, BAX, and CASP9 apoptotic genes.

Conclusion: WJMSCs-norCM has more anticancer activity than WJMSCs-hypoCM.

• Apoptosis
• Breast cancer
• Conditioned medium
• Hypoxia
• Wharton’s jelly-derived mesenchymal stem cells

• GSK-3α/β and ERK1/2 signaling pathways
• Mesenchymal stem cells
• apoptosis
• caspase 8 and 9
• stem cell-based therapy

• Apoptosis
• Colon cancer
• Secretome
• Umbilical cord stem cells

The tumor microenvironment (TME) plays a critical role in tumorigenesis and is composed of different cellular components, including immune cells and mesenchymal stromal cells (MSCs). In this review, we will discuss MSCs in the TME setting and more specifically their interactions with immune cells and how they can both inhibit (immunosurveillance) and favor (immunoediting) tumor growth. We will also discuss how MSCs are used as a therapeutic strategy in cancer. Due to their unique immunomodulatory properties, MSCs isolated from perinatal tissues are intensely explored as therapeutic interventions in various inflammatory-based disorders with promising results. However, their therapeutic applications in cancer remain for the most part controversial and, importantly, the interactions between administered perinatal MSC and immune cells in the TME remain to be clearly defined.

• cancer
• immunoediting
• immunosurveillance
• inflammation
• mesenchymal stromal cells
• perinatal
• placenta
• tumor microenvironment

Mesenchymal stem cells from Wharton's jelly of the human umbilical cord (hWJSCs), and the conditioned medium (hWJSC-CM) prepared from them, were shown to be tumoricidal on many cancers. However, these tumoricidal effects were observed in hWJSCs grown under normoxic conditions of 21% oxygen in the laboratory. Since oxygen concentrations in the stem cell niche or physiological microenvironment are hypoxic and help to maintain stemness properties, the objective of this work was to evaluate whether there were differences in the tumoricidal properties of hWJSC-CM grown in 21% O₂ (normoxic) or 5% O₂ (hypoxic) environments. The results showed that hWJSCs grown under normoxic or hypoxic conditions showed no distinct morphological differences in culture and remained positive in trilineage differentiation into adipocytes, osteocytes, and chondrocytes. Hypoxic hWJSCs expressed the mesenchymal stem cell surface markers CD105, CD90, CD73, CD146, and CD108 similar to normoxic hWJSCs but were negative for the hematopoietic markers CD14, CD19, CD34, CD45, CD117, and HLA-DR. Hypoxic hWJSC-CM produced a significantly greater reduction in cell viability and a significantly greater increase in apoptosis, oxidative stress, and lipid peroxidation in human lymphoma cells compared to normoxic hWJSC-CM. Hypoxic hWJSC-CM also produced significantly greater expression of immunogenic cell death (ICD) hallmarks such as surface-bound calreticulin, HSP70, HSP90, and high mobility group binding 1 proteins and significantly decreased expression of the defense molecules CD47 and PD-L1. This study showed that the tumoricidal effect of hypoxic hWJSC-CM was superior to normoxic hWJSC-CM and should be the preferred choice of preparing hWJSC-CM for the induction of ICD on lymphoma cells.

Keloid formation occurs in Caucasian, African, and Asian populations and is a severe psychosocial burden on patients. There is no permanent treatment for this problem as its pathogenesis is not properly understood. Furthermore, differences in keloid behavior between ethnic groups are not known. It has been hypothesized that keloids behave like benign tumors because of their uncontrolled growth. The present study evaluated the tumoricidal properties of human Wharton’s jelly stem cell-conditioned medium (hWJSC-CM) on fresh Asian keloid cells (AKCs).

Human Wharton’s jelly stem cells (hWJSCs) and AKCs were isolated based on our previous methods. hWJSCs and human skin fibroblasts (HSF) (controls) were used to collect hWJSC-CM and HSF-conditioned medium (HSF-CM). AKCs were treated with hWJSC-CM and HSF-CM in vitro and in vivo in a human keloid xenograft SCID mouse model. The inhibitory effect of hWJSC-CM on AKCs was tested in vitro using various assays and in vivo for attenuation/abrogation of AKC tumors created in a xenograft mouse model.

qRT-PCR analysis showed that the genes FN1, MMP1, and VCAN were significantly upregulated in AKCs and ANXA1, ASPN, IGFBP7, LGALS1, and PTN downregulated. AKCs exposed to hWJSC-CM in vitro showed significant decreases in cell viability and proliferation, increases in Annexin V-FITC+ cell numbers, interruptions of the cell cycle at Sub-G1 and G2/M phases, altered CD marker expression, downregulated anti-apoptotic-related genes, and upregulated pro-apoptotic and autophagy-related genes compared to controls. When AKCs were administered together with hWJSC-CM into immunodeficient mice there were no keloid tumors formed in 7 mice (n = 10) compared to the untreated control mice. When hWJSC-CM was injected directly into keloid tumors created in mice there were significant reductions in keloid tumor volumes and weights in 30 days.

hWJSC-CM inhibited the growth of AKCs in vitro and in xenograft mice, and it may be a potential novel treatment for keloids in the human. The specific molecule(s) in hWJSC-CM that induce the anti-keloid effect need to be identified, characterized, and tested separately in larger preclinical and clinical studies.

• Cell inhibition
• Characterization
• Human Wharton’s jelly stem cell-conditioned medium
• Keloid
• Keloid tumor volume and weight
• SCID mice

Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.

• anti-tumor activity
• cancer
• cell therapy
• mesenchymal stem cells
• therapeutic agents

• Animals
• Apoptosis
• Bone Marrow Cells/cytology
• Bone Marrow Cells/metabolism
• Cell Cycle
• Cells, Cultured
• Chemokine CXCL1/metabolism
• Coculture Techniques
• Cytokines/metabolism
• Humans
• K562 Cells
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Proto-Oncogene Proteins c-bcl-2/genetics
• Proto-Oncogene Proteins c-bcl-2/metabolism
• Rats
• Tissue Inhibitor of Metalloproteinase-1/metabolism
• bcl-2-Associated X Protein/genetics
• bcl-2-Associated X Protein/metabolism

• University of Tabriz

We speculate that exosomes derived from human umbilical cord mesenchymal stromal cells (HUC-MSCs) will accumulate within tumors and have the potential for both tumor location or drug delivery.

Methods: To determine proof of concept, HUC-MSC exosomes were labeled with an MRI contrast agent, gadolinium, or a near infrared dye. Exosome accumulation within ectopic osteosarcoma tumor-bearing mice was determined by 14.1 T MRI or bioimaging over 24-48 h after injection. In vitro studies examine the accumulation and physiological effect of exosomes on human and mouse osteosarcoma cell lines by MTT assay, confocal microscopy, and flow cytometry.

Results: Systemic HUC-MSC exosomes accumulated continuously in tumor over a 24-48 h post-injection period. In contrast, synthetic lipid nanoparticles accumulate in tumor only for the first 3 h post-injection.

Conclusion: These results suggest that HUC-MSCs exosomes accumulate within human or mouse osteosarcoma cells in vitro and in vivo over a 24 to 48 h after infusion.

• Extracellular vesicles
• ectopic osteosarcoma model
• gadolinium nanoparticle.
• non-invasive imaging

Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericytic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vascular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compression/contusion injury was induced at C7‐T1 in adult female rats, followed by an intravenous tail vein infusion 1 hour post‐SCI of (a) term‐birth human umbilical cord perivascular cells (HUCPVCs); (b) first‐trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrificed at 24 hours or 10 weeks post‐SCI and immunohistochemistry and ultrasound imaging were performed. Both term and FTM HUCPVC‐infused rats displayed improved (p < .05) grip strength compared with vehicle controls. However, only FTM HUCPVC‐infusion led to significant weight gain. All cell infusion treatments resulted in reduced glial scarring (p < .05). Cell infusion also led to increased axonal, myelin, and vascular densities (p < .05). Although post‐traumatic cavity volume was reduced with cell infusion, this did not reach significance. Taken together, we demonstrate selective long‐term functional recovery alongside histological improvements with HUCPVC infusion in a clinically relevant model of cervical SCI. Our findings highlight the potential of these cells for acute therapeutic intervention after SCI.

• Cervical spinal cord injury
• Mesenchymal stromal cells
• Vascular disruption

• Wharton's jelly stem cells
• differential expression
• mesenchymal stem cells
• single cell

• OVCAR3
• SKOV3
• cancer stem cells
• cell cycle
• cell migration
• gene expression
• stem cells
• tumor spheres

• Adult mesenchymal stem cells
• Experimental cancer cytotherapy
• Gene delivery vehicles
• Tumor microenvironment
• Umbilical cord matrix stem cells
• Wharton’s jelly

Mesenchymal stem cells (MSCs), derived from various tissues, are considered an ideal cell source for clinical use, among which MSCs from the umbilical cord exhibit advantages over those from adult tissues. In preclinical studies, mouse models and xenogeneic MSC treatment are most commonly used to imitate diseases and clinical practice, respectively. However, the efficiency of cross-species therapy remains controversial, making it difficult to elucidate the underlying mechanisms. Thus, allogeneic therapy may be more instructive and meaningful in clinical use. To confirm this hypothesis, the present study established a novel method for the isolation and expansion of MSCs from mouse umbilical cords (mUC-MSCs) to support in vivo experiments in mice. MSCs were isolated from mUCs and mouse bone marrow (mBM), and then identified by flow cytometry. The differences in mUC-MSCs and mBM-MSCs were analyzed using a growth curve and their differentiation ability. The results showed that the harvested cells exhibited general characteristics of MSCs and possessed the capacity for long-term culture. Despite having similar morphology and surface antigens to MSCs derived from mouse bone marrow, the mUC-MSCs showed differences in purification, proliferation, stem cell markers and differentiation. In addition to detailed characterization, the present study verified the presence of Toll-like receptor 3 (TLR3), an important component of immune responses, in mUC-MSCs. It was found that the activation of TLR3 upregulated the levels of stemness-related proteins, and enhanced the secretion and mRNA levels of inflammatory cytokines in the pre-treated mUC-MSCs. Collectively, the results of the present study provide further insight into the features of newly established mUC-MSCs, providing novel evidence for the selection of murine MSCs and their responses to TLR3 priming.

It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell’s divisions are asymmetric.

• Algorithms
• Cell Differentiation
• Cell Movement/physiology
• Cells, Cultured
• Humans
• Intestinal Mucosa/cytology
• Models, Biological
• Mutation
• Stem Cell Niche
• Stem Cells/cytology
• Stem Cells/physiology

• Division of Mathematical Sciences

• Animal models
• Chemical carcinogenesis
• Mammary cancer
• Rodents

• Animals
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/metabolism
• Cell Transformation, Neoplastic/pathology
• Female
• Mammary Neoplasms, Experimental/genetics
• Mammary Neoplasms, Experimental/metabolism
• Mammary Neoplasms, Experimental/pathology
• Mammary Neoplasms, Experimental/therapy
• Rats

• Dual tumor targeting
• Gene transduction
• HER2-positive tumors
• Immunoapoptotin
• Mesenchymal stem cells

• CANCER CELL INHIBITION
• CONDITIONED MEDIUM
• H2O2 SIGNALING
• HUMAN WHARTON'S JELLY STEM CELLS
• LYMPHOMA
• OXIDATIVE STRESS
• OXIDATIVE STRESS ENZYMES

• Cell death
• Cell proliferation
• IPA
• Ovarian cancer
• hWJSCs

• Adult mesenchymal stem cell
• HLAG-5
• Immunomodulation
• Microencapsulation
• Proliferation inhibition
• Type 1 diabetes mellitus

The human umbilical cord (UC) is an attractive source of mesenchymal stem cells (MSCs) with unique advantages over other MSC sources. They have been isolated from different compartments of the UC but there has been no rigorous comparison to identify the compartment with the best clinical utility. We compared the histology, fresh and cultured cell numbers, morphology, proliferation, viability, stemness characteristics and differentiation potential of cells from the amnion (AM), subamnion (SA), perivascular (PV), Wharton’s jelly (WJ) and mixed cord (MC) of five UCs. The WJ occupied the largest area in the UC from which 4.61 ± 0.57 x 10⁶ /cm fresh cells could be isolated without culture compared to AM, SA, PV and MC that required culture. The WJ and PV had significantly lesser CD40+ non-stem cell contaminants (26-27%) compared to SA, AM and MC (51-70%). Cells from all compartments were proliferative, expressed the typical MSC-CD, HLA, and ESC markers, telomerase, had normal karyotypes and differentiated into adipocyte, chondrocyte and osteocyte lineages. The cells from WJ showed significantly greater CD24+ and CD108+ numbers and fluorescence intensities that discriminate between MSCs and non-stem cell mesenchymal cells, were negative for the fibroblast-specific and activating-proteins (FSP, FAP) and showed greater osteogenic and chondrogenic differentiation potential compared to AM, SA, PV and MC. Cells from the WJ offer the best clinical utility as (i) they have less non-stem cell contaminants (ii) can be generated in large numbers with minimal culture avoiding changes in phenotype, (iii) their derivation is quick and easy to standardize, (iv) they are rich in stemness characteristics and (v) have high differentiation potential. Our results show that when isolating MSCs from the UC, the WJ should be the preferred compartment, and a standardized method of derivation must be used so as to make meaningful comparisons of data between research groups.

• Cell Culture Techniques/methods
• Cell Differentiation/physiology
• Female
• Fibroblasts/cytology
• Humans
• Mesenchymal Stem Cells/cytology
• Pluripotent Stem Cells/cytology
• Pregnancy
• Umbilical Cord/cytology