Three-dimensional culture of mesenchymal stem cells

Hong, Jong Kyu; Yun, Jisoo; Kim, Hyunyun; Kwon, Sang‐Mo

doi:10.1007/s13770-015-0005-7

Cited by 14 publications

(8 citation statements)

References 128 publications

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“…In the emerging field of tissue engineering, several alternative approaches have been proposed. Approaches of note include the development of 3D humanized BM structures in vitro 55 56 57 58 59 60 61 62 63 and the orthotopic graft of humanized BM scaffolds in mice 64 . Our approach has the advantage of combining both the complexity of the in vivo system with the easy anatomical accessibility of the humanized tissue graft.…”

Section: Discussionmentioning

confidence: 99%

Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging

Passaro

Abarrategi

Foster

et al. 2017

JoVE

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Human hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche, an intricate, multifactorial network of components producing cytokines, growth factors, and extracellular matrix. The ability of HSCs to remain quiescent, self-renew or differentiate, and acquire mutations and become malignant depends upon the complex interactions they establish with different stromal components. To observe the crosstalk between human HSCs and the human BM niche in physiological and pathological conditions, we designed a protocol to ectopically model and image a humanized BM niche in immunodeficient mice. We show that the use of different cellular components allows for the formation of humanized structures and the opportunity to sustain long-term human hematopoietic engraftment. Using two-photon microscopy, we can live-image these structures in situ at the single-cell resolution, providing a powerful new tool for the functional characterization of the human BM microenvironment and its role in regulating normal and malignant hematopoiesis.

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Section: Discussionmentioning

confidence: 99%

Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging

Passaro

Abarrategi

Foster

et al. 2017

JoVE

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“…In particular, we have shown that TMSCs can function as ‘smart cells’ capable of responding to extracellular calcium levels (Park et al , ), secreting more iPTH when the surrounding calcium concentration is lower. Nonetheless, massive losses of implanted stem cells and the subsequent reduction in therapeutic efficacy remains a major hurdle to implementing this approach (Hong et al , ; Lee et al , 2014), one that we previously tackled by embedding TMSCs in a Matrigel scaffold by simple physical mixing to regenerate parathyroid tissue (Park et al , ). Only when embedded in Matrigel did dTMSCs show parathyroid‐specific functions in a PTX rat model, controlling serum iPTH and iCa 2+ concentrations.…”

Section: Discussionmentioning

confidence: 99%

Sustained release of parathyroid hormone via in situ cross‐linking gelatin hydrogels improves the therapeutic potential of tonsil‐derived mesenchymal stem cells for hypoparathyroidism

Park

Lee

Jin

et al. 2017

J Tissue Eng Regen Med

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Biomimetic parathyroid regeneration with sustained release of parathyroid hormone (PTH) into the blood stream is a considerable challenge in hypoparathyroidism treatment. We recently reported that tonsil-derived mesenchymal stem cells (TMSCs), if these cells were both differentiated in vitro before implantation and incorporated into a scaffold Matrigel, are a good cell source for parathyroid regeneration in a parathyroidectomized (PTX) animal model. Here, we present a new strategy for improved clinical application that enhances the sustained release of PTH by controlling mechanical stiffness using in situ-forming gelatin-hydroxyphenyl propionic acid (GH) hydrogels (GHH). Differentiated TMSCs (dTMSCs) embedded in a GHH with a strength of 4.4 kPa exhibited the best sustained release of PTH and were the most effective in hypoparathyroidism treatment, showing improved blood calcium homeostasis compared with Matrigel-embedded dTMSCs. Interestingly, undifferentiated control TMSCs (cTMSCs) also released PTH in a sustained manner if incorporated into GHH. Collectively, these findings may establish a new paradigm for parathyroid regeneration that could ultimately evolve into an improved clinical application. Copyright © 2017 John Wiley & Sons, Ltd.

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“…Furthermore, clinical application of ASCs alone often results in problems such as low cell survival rates. [1][2][3] Considerable research has been carried out in the area of tissue engineering based regenerative medicine as a promising strategy in the treatment of damaged tissues and organs. [4,5] Tissue engineering has great potential and is likely to have a profound impact in the future.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

Jang

Park

et al. 2016

Macromolecular Bioscience

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In this study, human dental pulp stem cells (hDPSCs) are examined as a cellular source for bone tissue engineering using an in vivo-forming hydrogel. The hDPSCs are easily harvested in large quantities from extracted teeth. The stemness of harvested hDPSCs indicates their relative tolerance to ex vivo manipulation in culture. The in vitro osteogenic differentiation of hDPSCs is characterized using Alizarin Red S (ARS), von Kossa (VK), and alkaline phosphatase (ALP) staining. The solution of hDPSCs and a methoxy polyethylene glycol-polycaprolactone block copolymer (PC) is easily prepared by simple mixing at room temperature and in no more than 10 s it forms in vivo hydrogels after subcutaneous injection into rats. In vivo osteogenic differentiation of hDPSCs in the in vivo-forming hydrogel is confirmed by micro-computed tomography (CT), histological staining, and gene expression. Micro-CT analysis shows evidence of significant tissue-engineered bone formation in hDPSCs-loaded hydrogel in the presence of osteogenic factors. Differentiated osteoblasts in in vivo-forming hydrogel are identified by ARS and VK staining and are found to exhibit characteristic expression of genes like osteonectin, osteopontin, and osteocalcin. In conclusion, hDPSCs embedded in an in vivo-forming hydrogel may provide benefits as a noninvasive formulation for bone tissue engineering applications.

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Three-dimensional culture of mesenchymal stem cells

Cited by 14 publications

References 128 publications

Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging

Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging

Sustained release of parathyroid hormone via in situ cross‐linking gelatin hydrogels improves the therapeutic potential of tonsil‐derived mesenchymal stem cells for hypoparathyroidism

In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

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