Delivered adipose-derived stromal cells improve host-derived adipose tissue formation in composite constructs in vivo

In cartilage tissue engineering, as a cell source, adult stem cells are very attractive for clinical applications. Recent studies suggest that human adipose tissue-derived stromal cells (ASCs) have multilineage potential similar to bone marrow-derived stromal cells (BMSCs). ASCs are obtained from adipose tissue easily isolated by suction-assisted lipectomy in various body parts. Also, as one of major factors of cartilage tissue engineering, scaffolds have an important role in cartilage formation. Poly(L-lactide-co-ε-carprolactone) scaffolds have physiological activity, biodegradability, high cell affinity, and mechano-activity. The object of this study is cartilaginous tissue formation using highly elastic PLCL scaffolds and ASCs in vitro and in vivo. Poly(L-lactide-co-ε-carprolactone) copolymers were synthesized from lactide and ε-carprolactone in the presence of stannous octoate as catalyst. The scaffolds with 85% porosity and 300-500μm pore size were fabricated by gel-pressing method. ASCs were seeded on scaffolds and cultured for 21days in vitro. Cell/polymer constructs were characterized by reverse transcriptase-polymerase chain reaction for confirming differentiation to chondrocytes onto PLCL scaffolds. Also, for examining cartilaginous tissue formation in vivo, ASCs seeded scaffolds which were induced chondrogenesis for 2 weeks were implanted in nude mice subcutaneously for up to 8weeks. Histological studies showed that implants partially developed cartilaginous tissue within lacunae. And there was an accumulation of sulfated glycoaminoglycans. Immunohistochemical analysis revealed that implants were positively stained for specific extracellular matrix. These results indicate that ASCs and PLCL scaffols could be used to cartilage tissue engineering.

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In vivo Adipose Tissue Regeneration by Adipose-Derived Stromal Cells Isolated from GFP Transgenic Mice

Cells Tissues Organs ◽

10.1159/000110805 ◽

2008 ◽

Vol 187 (3) ◽

pp. 177-185 ◽

Cited By ~ 39

Author(s):

Hiroshi Mizuno ◽

Yurie Itoi ◽

Satoko Kawahara ◽

Rei Ogawa ◽

Satoshi Akaishi ◽

...

Keyword(s):

Adipose Tissue ◽

Transgenic Mice ◽

Tissue Regeneration ◽

Stromal Cells ◽

Adipose Derived Stromal Cells

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hPER3 promotes adipogenesis via hHSP90AA1-mediated inhibition of Notch1 pathway

Cell Death and Disease ◽

10.1038/s41419-021-03584-0 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Xinxing Wan ◽

Liyong Zhu ◽

Liling Zhao ◽

Lin Peng ◽

Jing Xiong ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Stromal Cells ◽

Critical Role ◽

Human Adipose Tissue ◽

Positive Role ◽

Positive Regulator ◽

Adipose Derived Stromal Cells

AbstractThe period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance. Molecularly, hPER3 does not interact with hPPARγ, but represses Notch1 signaling pathway to enhance adipogenesis by interacting with hHSP90AA1, which is able to combine with the promoter of hNotch1 and inactivate its expression. Thus, our study revealed hPER3 as a critical positive regulator of hADSCs adipogenesis, which was different from the other types of cells, providing a critical role of it in treating obesity.

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Perfusion bioreactor culture of adipose-derived stromal cells on decellularized adipose tissue scaffolds enhances in vivo regeneration

10.1101/2020.04.10.036194 ◽

2020 ◽

Author(s):

Tim Tian Y. Han ◽

Lauren E. Flynn

Keyword(s):

Adipose Tissue ◽

Stromal Cells ◽

Unmet Need ◽

Perfusion Bioreactor ◽

Bioreactor Culture ◽

Adipose Tissue Engineering ◽

Adipose Derived Stromal Cells ◽

The Impact

AbstractAdipose tissue engineering holds promise to address the unmet need in plastic and reconstructive surgery for strategies that promote the stable and predictable regeneration of adipose tissue for volume augmentation applications. Previous studies have demonstrated that decellularized adipose tissue (DAT) scaffolds can provide a pro-adipogenic microenvironment, and that seeding with adipose-derived stromal cells (ASCs) can enhance in vivo angiogenesis and adipogenesis within DAT implants. Recognizing that bioreactor systems can promote cell expansion and infiltration on tissue-engineered scaffolds, this study evaluated the effects of culturing human ASCs on DAT scaffolds within a perfusion bioreactor. Using this system, the impact of both shear stress stimulation and hypoxic preconditioning were explored in vitro and in vivo. Initial studies compared the effects of 14 days of culture within the perfusion bioreactor under 2% O2 or ~20% O2 on human ASC expansion and hypoxia inducible factor 1 alpha (HIF-1α) expression in vitro relative to static cultured controls. The findings indicated that culturing within the bioreactor under 2% O2 significantly increased ASC proliferation on the DAT, with a higher cell density observed in the scaffold periphery. HIF-1α expression was significantly higher when the scaffolds were cultured under 2% O2. Subsequent characterization in a subcutaneous implant model in athymic nude mice revealed that in vivo angiogenesis and adipogenesis were markedly enhanced when the ASCs were cultured on the DAT within the perfusion bioreactor under 2% O2 for 14 days prior to implantation relative to the other culture conditions, as well as additional freshly-seeded and unseeded DAT control groups. Overall, dynamic culture within the perfusion bioreactor system under hypoxia represents a promising approach for preconditioning ASCs on DAT scaffolds to enhance their capacity to stimulate blood vessel formation and infiltration, as well as host-derived adipose tissue regeneration.

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Preconditioning Human Adipose-Derived Stromal Cells on Decellularized Adipose Tissue Scaffolds Within a Perfusion Bioreactor Modulates Cell Phenotype and Promotes a Pro-regenerative Host Response

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.642465 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tim Tian Y. Han ◽

John T. Walker ◽

Aaron Grant ◽

Gregory A. Dekaban ◽

Lauren E. Flynn

Keyword(s):

Adipose Tissue ◽

Stromal Cells ◽

Soft Tissue Augmentation ◽

Cell Phenotype ◽

Perfusion Bioreactor ◽

Bioreactor Culture ◽

Arginase 1 ◽

Adipose Derived Stromal Cells ◽

Human Ascs

Cell-based therapies involving the delivery of adipose-derived stromal cells (ASCs) on decellularized adipose tissue (DAT) scaffolds are a promising approach for soft tissue augmentation and reconstruction. Our lab has recently shown that culturing human ASCs on DAT scaffolds within a perfusion bioreactor prior to implantation can enhance their capacity to stimulate in vivo adipose tissue regeneration. Building from this previous work, the current study investigated the effects of bioreactor preconditioning on the ASC phenotype and secretory profile in vitro, as well as host cell recruitment following implantation in an athymic nude mouse model. Immunohistochemical analyses indicated that culturing within the bioreactor increased the percentage of ASCs co-expressing inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1), as well as tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10), within the peripheral regions of the DAT relative to statically cultured controls. In addition, bioreactor culture altered the expression levels of a range of immunomodulatory factors in the ASC-seeded DAT. In vivo testing revealed that culturing the ASCs on the DAT within the perfusion bioreactor prior to implantation enhanced the infiltration of host CD31+ endothelial cells and CD26+ cells into the DAT implants, but did not alter CD45+F4/80+CD68+ macrophage recruitment. However, a higher fraction of the CD45+ cell population expressed the pro-regenerative macrophage marker CD163 in the bioreactor group, which may have contributed to enhanced remodeling of the scaffolds into host-derived adipose tissue. Overall, the findings support that bioreactor preconditioning can augment the capacity of human ASCs to stimulate regeneration through paracrine-mediated mechanisms.

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