Nanocellulose‐Reinforced Hydroxyapatite Nanobelt Membrane as a Stem Cell Multi‐Lineage Differentiation Platform for Biomimetic Construction of Bioactive 3D Osteoid Tissue In Vitro

e16055 Background: The introduction of VEGF/VEGFR- and mTOR, and immune checkpoint-targeted agents has radically changed metastatic RCC treatment; however, predictive biomarkers are still lacking and the potential for curative impact of such treatments in earlier disease stages is hotly debated. To identify potential diagnostic, prognostic, and predictive biomarkers, we developed patient-derived preclinical RCC models based on PDX obtained from freshly dissociated cancer tissues and combining isolation of cell populations endowed with self renewal and multi-lineage differentiation abilities (CSC). Methods: 182 surgical RCC specimens (clear cell, n = 110; papillary type I/II, n = 23, chromophobe/oncocytoma, n = 26, other, n = 23; stage I-III, n = 124, stage IV, n = 28, n/a n = 30) were collected; tumor spheroids were obtained and characterized in 57 cases, using a stem-cell isolating medium supplemented with EGF/b-FGF; 30 cancer samples were orthotopically injected in immunocompromised mice and were able to engraft in 67% of cases (G3-G4 cases more frequently than G1-G2 cases, p = 0.04). Results: PDX tumors recapitulated histological appearance, sarcomatoid features when they were present, and tumor heterogeneity of their human counterpart; interestingly, PDX engraftment was significantly correlated with shorter DFS in the corresponding patient population (p = 0.12). We conducted proteomic analysis by Reverse Phase Protein Array (RPPA) in 21 patient-derived CSC models in vitro: a panel of established (HIF, VEGFR, mTOR) and novel (EGFR(Y1148)), AKT, PI3K) oncogenic signals were deregulated in our isolated cell populations; molecular endpoints were correlated with grading and with angiogenesis and mTOR pathways (p < 0.05). Data analysis is ongoing to ascertain whether specific RPPA-signatures can potentially complement clinical prognostic information and suggest candidate biomarkers and potential targets for therapy. Conclusions: In the era of personalized therapy, the combined use of PDX and RPPA from tumor specimens may be very useful for drug testing and patient stratification in RCC.

Download Full-text

Electro-Acupuncture Promotes Endogenous Multipotential Mesenchymal Stem Cell Mobilization into the Peripheral Blood

Cellular Physiology and Biochemistry ◽

10.1159/000443101 ◽

2016 ◽

Vol 38 (4) ◽

pp. 1605-1617 ◽

Cited By ~ 4

Author(s):

Lizhen Liu ◽

Qin Yu ◽

Kaimin Hu ◽

Binsheng Wang ◽

Yiran Zhang ◽

...

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Peripheral Blood ◽

Control Groups ◽

Adult Rats ◽

Differentiation Potential ◽

Lineage Differentiation ◽

Stromal Cell Derived Factor ◽

Cell Mobilization

Background/Aims: Mobilization of endogenous stem cells is an appealing strategy for cell therapy However, there is little evidence for reproducible, effective methods of mesenchymal stem cell (MSC) mobilization. In the present study, we investigated the mobilizing effect of electro-acupuncture (EA) on endogenous MSCs. Methods: Normal adult rats were randomly divided into six groups, namely, EA for 14 days (EA14d), sham EA14d, EA21d, sham EA21d and matched control groups. MSC mobilization efficiency was determined by colony-forming unit fibroblast (CFU-F) assays. Mobilized peripheral blood (PB)-derived MSCs were identified by immunophenotype and multi-lineage differentiation potential. Results: CFU-F frequency was significantly increased in the PB of EA14d rats compared with the sham EA and control groups. Moreover, the number of CFU-Fs was increased further in the EA21d group. MSCs derived from EA-mobilized PB were positive for CD90 and CD44, but negative for CD45. Additionally, these cells could differentiate into adipocytes, osteoblasts, chondrocytes and neural-like cells in vitro. Finally, stromal cell-derived factor-1α (SDF-1α) was increased in the PB of rats subjected to EA, and the migration of MSCs was improved in response to SDF-1α. Conclusions: MSCs with multi-lineage differentiation potential can be mobilized by EA. Our data provide a promising strategy for MSC mobilization.

Download Full-text

Comparative Study of Biological Characteristics, and Osteoblast Differentiation of Mesenchymal Stem Cell Established From Camelus Dromedaries Skeletal Muscle, Dermal Skin, and Adipose Tissues

10.20944/preprints202102.0614.v1 ◽

2021 ◽

Author(s):

Young-Bum Son ◽

Yeon Ik Jeong ◽

Yeon Woo Jeong ◽

Mohammad Shamim Hossein ◽

Alex Tinson ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Stem Cell ◽

Comparative Study ◽

Osteoblast Differentiation ◽

Biological Characteristics ◽

Adipose Tissues ◽

Differentiation Capacity ◽

Lineage Differentiation

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renew capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was no significant difference in all groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the ALP activity and calcium content was significantly decreased in A-MSCs as compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primally established MSCs from the single camel and demonstrated their comparative characteristics including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

Download Full-text

Comparative Study of Biological Characteristics, and Osteoblast Differentiation of Mesenchymal Stem Cell Established from Camelus dromedarius Skeletal Muscle, Dermal Skin, and Adipose Tissues

Animals ◽

10.3390/ani11041017 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1017

Author(s):

Young-Bum Son ◽

Yeon Ik Jeong ◽

Yeon Woo Jeong ◽

Mohammad Shamim Hossein ◽

Alex Tinson ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Stem Cell ◽

Comparative Study ◽

Osteoblast Differentiation ◽

Biological Characteristics ◽

Adipose Tissues ◽

Differentiation Capacity ◽

Lineage Differentiation

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renewal capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was not significantly difference in any of the groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the alkaline phosphatase (ALP) activity and calcium content significantly decreased in A-MSCs compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primarily established MSCs from the single camel and demonstrated their comparative characteristics, including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

Download Full-text

Epidermal cell lineage

Biochemistry and Cell Biology ◽

10.1139/o98-088 ◽

1998 ◽

Vol 76 (6) ◽

pp. 889-898 ◽

Cited By ~ 27

Author(s):

Kursad Turksen ◽

Tammy-Claire Troy

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Skin Diseases ◽

Cell Model ◽

Embryonic Stem ◽

Cell Lineage ◽

Model System ◽

Epidermal Stem Cells ◽

Lineage Differentiation

The epidermis is a stratified squamous epithelium, which is under a constant state of proliferation, commitment, differentiation, and elimination so that the functional integrity of the tissue is maintained. The intact epidermis has the ability to respond to diverse environmental stimuli by continuous turnover to maintain its normal homeostasis throughout an organism's life. This is achieved by a tightly regulated balance between stem cell self-renewal and the generation of a population of cells that undergo a limited number of more rapid (amplifying) transit divisions before giving rise to nonproliferative, terminally differentiating cells. This process makes it an excellent model system to study lineage, commitment, and differentiation, although neither the identity of epidermal stem cells nor the precise steps and regulators that lead to mature epidermal cells have yet been determined. Furthermore, the identities of genes that initiate epidermal progenitor commitment to the epidermal lineage, from putative epidermal stem cells, are unknown. This is mainly due to the lack of an in vitro model system, as well as the lack of specific reagents, to study the early events in epidermal lineage. Our recent development of a differentiating embryonic stem cell model for epidermal lineage now offers the opportunity to analyze the factors that regulate epidermal lineage. These studies will provide new insight into epidermal lineage and lead to a better understanding of various hyperproliferative skin diseases such as psoriasis and cancer.Key words: epidermis, lineage differentiation, embryonic stem cells.

Download Full-text