Abstract:[Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific
plan of care based on a patient’s medical status. The intrinsic self-renewing,
multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells
offer great promise in the treatment of numerous autoimmune, degenerative, and
graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells
represent a therapeutic fortune in regenerative medicine. The aim of this review is to
discuss… Show more
“…Indeed, there was evidence for the critical role of ADSCs in maintaining the structure of skin tissue, even as a physiological response to local injury or as rejuvenating mechanisms by seeding younger cells to the outer of the epidermis [5,[15][16][17]. Identified within the basal layer where they self-renewed and differentiated to continuously settle the epidermis with keratinocytes, fibroblasts, and melanocytes [18,19], these cells might influence the physiological characteristics of the injured skin and presented with a great ability in migration and were recruited into wounded sites [11,[20][21][22]. ADSCs have been shown to differentiate into keratinocytes, dermal fibroblasts (DF), and other skin components [15,23,24].…”
Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.
“…Indeed, there was evidence for the critical role of ADSCs in maintaining the structure of skin tissue, even as a physiological response to local injury or as rejuvenating mechanisms by seeding younger cells to the outer of the epidermis [5,[15][16][17]. Identified within the basal layer where they self-renewed and differentiated to continuously settle the epidermis with keratinocytes, fibroblasts, and melanocytes [18,19], these cells might influence the physiological characteristics of the injured skin and presented with a great ability in migration and were recruited into wounded sites [11,[20][21][22]. ADSCs have been shown to differentiate into keratinocytes, dermal fibroblasts (DF), and other skin components [15,23,24].…”
Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.
“…Currently, mesenchymal stromal/stem cells (MSCs) derived from various sources (tissues) are often used for cell based therapies to treat a variety of diseases [ 1 ]. Such applications typically require large numbers of cells produced by in vitro expansion of cells via continuing passaging.…”
Expansion of mesenchymal stromal/stem cells (MSCs) used in clinical practices may be associated with accumulation of genetic instability. Understanding temporal and mechanistic aspects of this process is important for improving stem cell therapy protocols. We used γH2AX foci as a marker of a genetic instability event and quantified it in MSCs that undergone various numbers of passage (3-22). We found that γH2AX foci numbers increased in cells of late passages, with a sharp increase at passage 16-18. By measuring in parallel foci of ATM phosphorylated at Ser-1981 and their co-localization with γH2AX foci, along with differentiating cells into proliferating and resting by using a Ki67 marker, we conclude that the sharp increase in γH2AX foci numbers was ATM-independent and happened predominantly in proliferating cells. At the same time, gradual and moderate increase in γH2AX foci with passage number seen in both resting and proliferating cells may represent a slow, DNA double-strand break related component of the accumulation of genetic instability in MSCs. Our results provide important information on selecting appropriate passage numbers exceeding which would be associated with substantial risks to a patient-recipient, both with respect to therapeutic efficiency and side-effects related to potential neoplastic transformations due to genetic instability acquired by MSCs during expansion.
“…9,23,30 While the majority of adult tissues have been shown to contain resident MSCs, studies have illustrated that MSC numbers decline with increasing age. 24 Human MSCs, including those isolated from adipose (hADSCs) and bone marrow–derived (hBMSCs) tissue, have demonstrated varying degrees of therapeutic efficacy in preclinical models and human clinical trials. Reduced pain 5 and/or improved chondroprotection has been observed after MSC treatment.…”
Background
Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations.
Purpose
To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation.
Study Design
Controlled laboratory study.
Methods
MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated.
Results
The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics—(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)—and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 106 ± 3.7 × 105 and 1.6 × 106 ± 4.7 × 105 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin (P = .025), aggrecan (P < .0001), and collagen type 2 (P = .044) gene expression compared with hADSCs, respectively, after culture in differentiation medium. Moreover, both hAECs and hAMSCs produced significantly greater quantities of mineralized (P < .0001) and cartilaginous (P = .0004) matrix at earlier time points compared with hADSCs when cultured under identical osteogenic and chondrogenic differentiation conditions, respectively.
Conclusion
Amnion-derived MSCs demonstrate a greater differentiation potential toward bone and cartilage compared with hADSCs.
Clinical Relevance
Amniotic MSCs may be the source of choice in the regenerative treatment of bone or osteochondral musculoskeletal disease. They show significantly higher yields and better differentiation toward these tissues than MSCs derived from adipose.
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