scholarly journals Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response

2019 ◽  
Vol 20 (7) ◽  
pp. 1716 ◽  
Author(s):  
Gauri Tendulkar ◽  
Sabrina Ehnert ◽  
Vrinda Sreekumar ◽  
Tao Chen ◽  
Hans-Peter Kaps ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Types ◽  
Bmp Signaling ◽  
Anabolic Response ◽  
Health And Social Care ◽  
Intervertebral Disc Regeneration ◽  
Exogenous Delivery

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In this study, we analyzed the influence on anabolic response, by delivering synthetic Link N encoding mRNA into primary human chondrocytes and mesenchymal stromal cells (SCP1 cells), Furthermore, both cell types were seeded on knitted titanium scaffolds, and the influence of Link N peptide mRNA for possible tissue engineering applications was investigated. Synthetic modified Link N mRNA was efficiently delivered into both cell types and cell transfection resulted in an enhanced expression of aggrecan, Sox 9, and type II collagen with a decreased expression of type X collagen. Interestingly, despite increased expression of BMP2 and BMP7, BMP signaling was repressed and TGFβ signaling was boosted by Link N transfection in mesenchymal stromal cells, suggesting possible regulatory mechanisms. Thus, the exogenous delivery of Link N peptide mRNA into cells augmented an anabolic response and thereby increased extracellular matrix synthesis. Considering these findings, we suppose that the cultivation of cells on knitted titanium scaffolds and the exogenous delivery of Link N peptide mRNA into cells could mechanically support the stability of tissue-engineered constructs and improve the synthesis of extracellular matrix by seeded cells. This method can provide a potent strategy for articular cartilage and intervertebral disc regeneration.

scholarly journals Augmentation of Dermal Wound Healing by Adipose Tissue-Derived Stromal Cells (ASC)

2018 ◽  
Vol 5 (4) ◽  
pp. 91 ◽  
Author(s):  
Joris van Dongen ◽  
Martin Harmsen ◽  
Berend van der Lei ◽  
Hieronymus Stevens
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Randomized Clinical Trials ◽  
Cell Types ◽  
Matrix Remodeling ◽  
Skin Wound Healing ◽  
Dermal Wound Healing ◽  
Dermal Wound

The skin is the largest organ of the human body and is the first line of defense against physical and biological damage. Thus, the skin is equipped to self-repair and regenerates after trauma. Skin regeneration after damage comprises a tightly spatial-temporally regulated process of wound healing that involves virtually all cell types in the skin. Wound healing features five partially overlapping stages: homeostasis, inflammation, proliferation, re-epithelization, and finally resolution or fibrosis. Dysreguled wound healing may resolve in dermal scarring. Adipose tissue is long known for its suppressive influence on dermal scarring. Cultured adipose tissue-derived stromal cells (ASCs) secrete a plethora of regenerative growth factors and immune mediators that influence processes during wound healing e.g., angiogenesis, modulation of inflammation and extracellular matrix remodeling. In clinical practice, ASCs are usually administered as part of fractionated adipose tissue i.e., as part of enzymatically isolated SVF (cellular SVF), mechanically isolated SVF (tissue SVF), or as lipograft. Enzymatic isolation of SVF obtained adipose tissue results in suspension of adipocyte-free cells (cSVF) that lack intact intercellular adhesions or connections to extracellular matrix (ECM). Mechanical isolation of SVF from adipose tissue destructs the parenchyma (adipocytes), which results in a tissue SVF (tSVF) with intact connections between cells, as well as matrix. To date, due to a lack of well-designed prospective randomized clinical trials, neither cSVF, tSVF, whole adipose tissue, or cultured ASCs can be indicated as the preferred preparation procedure prior to therapeutic administration. In this review, we present and discuss current literature regarding the different administration options to apply ASCs (i.e., cultured ASCs, cSVF, tSVF, and lipografting) to augment dermal wound healing, as well as the available indications for clinical efficacy.

scholarly journals POSTNATAL EXTRA-EMBRYONIC TISSUES AS A SOURCE OF MULTIPLE CELL TYPES FOR REGENERATIVE MEDICINE APPLICATIONS

2017 ◽  
Vol 39 (3) ◽  
pp. 186-190 ◽  
Author(s):  
O S Gubar ◽  
A I Rodnichenko ◽  
R G Vasylie ◽  
A V Zlatska ◽  
D O Zubov
Keyword(s):  
Regenerative Medicine ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Population Doubling ◽  
Embryonic Tissues ◽  
Chorionic Membrane ◽  
Multiple Cell

Aim: We aimed to isolate and characterize the cell types which could be obtained from postnatal extra-embryonic tissues. Materials and Methods: Fresh tissues (no more than 12 h after delivery) were used for enzymatic or explants methods of cell isolation. Obtained cultures were further maintained at 5% oxygen. At P3 cell phenotype was assessed by fluorescence-activated cell sorting, population doubling time was calculated and the multilineage differentiation assay was performed. Results: We have isolated multiple cell types from postnatal tissues. Namely, placental mesenchymal stromal cells from placenta chorionic disc, chorionic membrane mesenchymal stromal cells (ChM-MSC) from free chorionic membrane, umbilical cord MSC (UC-MSC) from whole umbilical cord, human umbilical vein endothelial cells (HUVEC) from umbilical vein, amniotic epithelial cells (AEC) and amniotic MSC (AMSC) from amniotic membrane. All isolated cell types displayed high proliferation rate together with the typical MSC phenotype: CD73+CD90+CD105+CD146+CD166+CD34-CD45-HLA-DR-. HUVEC constitutively expressed key markers CD31 and CD309. Most MSC and AEC were capable of osteogenic and adipogenic differentiation. Conclusion: We have shown that a wide variety of cell types can be easily isolated from extra-embryonic tissues and expanded ex vivo for regenerative medicine applications. These cells possess typical MSC properties and can be considered an alternative for adult MSC obtained from bone marrow or fat, especially for allogeneic use.

scholarly journals Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration

2019 ◽  
Vol 7 ◽  
Author(s):  
Peng Hu ◽  
Qinxin Yang ◽  
Qi Wang ◽  
Chenshuo Shi ◽  
Dali Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Messenger Rna ◽  
Cell Types ◽  
Skin Wound ◽  
Effector Proteins ◽  
Skin Wound Healing ◽  
New Research

Abstact Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types, growth factors, extracellular matrix (ECM), nerves, and blood vessels. Mesenchymal stromal cells (MSCs) take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans. Exosomes, which are among the key products MSCs release, mimic the effects of parental MSCs. They can shuttle various effector proteins, messenger RNA (mRNA) and microRNAs (miRNAs) to modulate the activity of recipient cells, playing important roles in wound healing. Moreover, using exosomes avoids many risks associated with cell transplantation. Therefore, as a novel type of cell-free therapy, MSC-exosome -mediated administration may be safer and more efficient than whole cell. In this review, we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration. In addition, we address the hypothesis of MSCs microenvironment extracellular vesicles (MSCs-MEVs) or MSCs microenvironment exosomes (MSCs-MExos) that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications. This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.

scholarly journals Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells

2017 ◽  
Vol 45 (11) ◽  
pp. 2637-2646 ◽  
Author(s):  
Natasha Topoluk ◽  
Richard Hawkins ◽  
John Tokish ◽  
Jeremy Mercuri
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Chondrogenic Differentiation ◽  
Cell Types ◽  
Cell Counting ◽  
Gene Transcript ◽  
Differentiation Potential ◽  
Musculoskeletal Tissue ◽  
Cell Groups ◽  
And Cartilage

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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