Human Mesenchymal Stromal Cells from Different Sources Diverge in Their Expression of Cell Surface Proteins and Display Distinct Differentiation Patterns
Abstract:When germ-free cell cultures became a laboratory routine, hopes were high for using this novel technology for treatment of diseases or replacement of cells in patients suffering from injury, inflammation, or cancer or even refreshing cells in the elderly. Today, more than 50 years after the first successful bone marrow transplantation, clinical application of hematopoietic stem cells is a routine procedure, saving the lives of many every day. However, transplanting other than hematopoietic stem and progenitor … Show more
“…However, hematopoietic cell markers (such as CD45, CD34 and CD19) were not expressed. All the surface markers expression detected in the three tissues-derived MSCs conformed to the criteria of MSCs established before 19 and no comparable differences were observed among UC-MSC, Ad-MSC and BM-MSC.Figure 2Immunophenotype of MSCs. UC-MSC ( A ), Ad-MSC ( B ) and BM-MSC ( C ) were labeled with antibodies against the indicated antigens, and analyzed by flow cytometry.…”
Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and cellular therapy due to their multi-lineage differentiation potential and immunomodulatory function. The applicability of MSCs also depends on their cellular sources and in vivo functions. Here in this study, we systematically compared the morphologic characteristics, immunophenotypes and the adipogenic differentiation of MSCs derived from umbilical cord (UC), adipose tissue (Ad) and bone marrow (BM). We found that the three tissues-derived MSCs displayed decreased adipogenic capacity in the order: Ad-MSC > BM-MSC > UC-MSC, and no morphologic and immunophenotypic differences were observed. Mechanistic investigation revealed a miR-301b~miR-130b—PPARγ axis, whose expression pattern in UC-MSC, Ad-MSC and BM-MSC significantly correlates with their adipogenic capacity. Our results come up with a potential mechanism to elucidate the differential adipogenesis of Ad-MSC, BM-MSC and UC-MSC, which would provide instructional advice for which source of MSCs to choose according to a certain clinical purpose. Furthermore, the miR-301b~miR-130b—PPARγ axis may also be used as a potential therapeutic target for the disorders associated with MSCs-mediated abnormal adipogenesis.
“…However, hematopoietic cell markers (such as CD45, CD34 and CD19) were not expressed. All the surface markers expression detected in the three tissues-derived MSCs conformed to the criteria of MSCs established before 19 and no comparable differences were observed among UC-MSC, Ad-MSC and BM-MSC.Figure 2Immunophenotype of MSCs. UC-MSC ( A ), Ad-MSC ( B ) and BM-MSC ( C ) were labeled with antibodies against the indicated antigens, and analyzed by flow cytometry.…”
Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and cellular therapy due to their multi-lineage differentiation potential and immunomodulatory function. The applicability of MSCs also depends on their cellular sources and in vivo functions. Here in this study, we systematically compared the morphologic characteristics, immunophenotypes and the adipogenic differentiation of MSCs derived from umbilical cord (UC), adipose tissue (Ad) and bone marrow (BM). We found that the three tissues-derived MSCs displayed decreased adipogenic capacity in the order: Ad-MSC > BM-MSC > UC-MSC, and no morphologic and immunophenotypic differences were observed. Mechanistic investigation revealed a miR-301b~miR-130b—PPARγ axis, whose expression pattern in UC-MSC, Ad-MSC and BM-MSC significantly correlates with their adipogenic capacity. Our results come up with a potential mechanism to elucidate the differential adipogenesis of Ad-MSC, BM-MSC and UC-MSC, which would provide instructional advice for which source of MSCs to choose according to a certain clinical purpose. Furthermore, the miR-301b~miR-130b—PPARγ axis may also be used as a potential therapeutic target for the disorders associated with MSCs-mediated abnormal adipogenesis.
“…Among these, mesenchymal stem/stromal cells (MSCs) have been the most abundantly used. MSCs have multi‐lineage differentiation potential and can be isolated from various tissue sources including bone marrow, adipose tissue, and umbilical cord . In addition to their osteogenic, chondrogenic, and adipogenic differentiation potential, MSCs can orchestrate the function of other cells by paracrine signalling or even endocrine mechanisms .…”
Section: Advances In Treatment Of Local Muscle Injuriesmentioning
Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.
“…Thereafter, a large number of studies correlated MSC phenotypic features and investigated the therapeutic potential of MSCs. Elahi et al reported that the term "mesenchymal stem cell" yielded more than 357,000 hits in Google Scholar (Google Scholar; July 2015) [30]. Colonyforming cells have since been called "mesenchymal stem cells" or "mesenchymal stromal cells."…”
Section: Mscs Are Defined As Self-renewing Populations In Multiple Ormentioning
confidence: 99%
“…Interestingly, "stemness" has been shown to be a stricter term for MSCs involved in tissue repair (Fig. 2) [30]. Recently, "skeletal stem cells (SSCs)" has supplanted the term "tissue stem cells" as the new term for these cells [31,32].…”
Section: Mscs Are Defined As Self-renewing Populations In Multiple Ormentioning
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