Improving Lentiviral Transduction of Human Adipose-Derived Mesenchymal Stem Cells

Collon, Kevin; Gallo, Matthew C.; Bell, John; Chang, Sharon B.; Rodman, Jack; Sugiyama, Osamu; Kohn, Donald B.; Lieberman, Jay R.

doi:10.1089/hum.2022.117

Cited by 6 publications

(6 citation statements)

References 36 publications

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“…Viral vectors have been increasingly explored as gene delivery tools for induction of long-term transgene expression in MSCs, widening the potential of these cells as gene therapy agents [35]. Ranging from cardiac regeneration [36, 37] to targeted treatment of bone defects [38], autoimmune disorders [39] and cancer applications [40], genetic manipulation of MSCs has proven to be a promising tool in tissue engineering and regenerative medicine.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, transduction enhancing materials made a significant different in engineering MSCs in capsules. Different transduction enhancers have previously been investigated in the context of genetic manipulation of MSCs [35, 67]. These reagents mainly neutralize the natural surface charge of cells, enhancing viral adsorption by the presence of polycations.…”

Section: Discussionmentioning

confidence: 99%

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3D Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor

Teryek

Jadhav

Bento

et al. 2023

Preprint

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Microencapsulation of human mesenchymal stromal cells (MSCs) via electrospraying has been well documented in tissue engineering and regenerative medicine. Herein, we report the use of microencapsulation, via electrospraying, for MSC expansion using a commercially available hydrogel that is durable, optimized to MSC culture, and enzymatically degradable for cell recovery. Critical parameters of the electrospraying encapsulation process such as seeding density, correlation of microcapsule output with hydrogel volume, and applied voltage were characterized to consistently fabricate cell-laden microcapsules of uniform size. Upon encapsulation, we then verified ~ 10x expansion of encapsulated MSCs within a vertical-wheel bioreactor and the preservation of critical quality attributes such as immunophenotype and multipotency after expansion and cell recovery. Finally, we highlight the genetic manipulation of encapsulated MSCs as an example of incorporating bioactive agents in the capsule material to create new compositions of MSCs with altered phenotypes.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

3D Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor

Teryek

Jadhav

Bento

et al. 2023

Preprint

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“…No impact on RT kinetics or lentiviral integration profile was identified in this study. Several studies have demonstrated the applicability of previously described TEs to other cell and vector types, 10 , 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 suggesting some commonalities in their mechanisms of action. It would be of interest to conduct further studies to determine whether GSK2622391 is also able to enhance transduction in other cell or vector types.…”

Section: Discussionmentioning

confidence: 97%

“…Several TEs have been shown to work synergistically. 17 While much of the focus has been on TEs for lentiviral transduction of HSCs, their use has also been reported in other cell types, including T cells, 14 , 18 , 19 , 20 , 21 mesenchymal stem cells (MSCs), 10 , 22 and dendritic cells, 23 and with other types of vectors including adenovirus 23 and α-retrovirus. 17 …”

Section: Introductionmentioning

confidence: 99%

“…Aside from their transduction-enhancing activity, there are other considerations for introduction of a TE into cell therapy manufacturing. Although polybrene has been widely used because of its low cost, ease of use, and efficacy in many cell types, it is also toxic to cells at higher concentrations and has been shown to alter cellular characteristics, including differentiation and proliferation of MSCs 22 and T cells. 18 RetroNectin resulted in a change in the proportion of T cell memory subtypes, 18 PGE2 reduced CD90 + long-term repopulating HSCs, 17 and rapamycin reduced cell-cycle progression and proliferation in HSCs.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a small molecule for enhancing lentiviral transduction of T cells

Malach,

Kay,

Tinworth

et al. 2023

Molecular Therapy - Methods & Clinical Development

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Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Taheri,

Tehrani,

Dehghani

et al. 2024

Medicinal Research Reviews

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Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC‐mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

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Improving Lentiviral Transduction of Human Adipose-Derived Mesenchymal Stem Cells

Cited by 6 publications

References 36 publications

3D Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor

3D Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor

Identification of a small molecule for enhancing lentiviral transduction of T cells

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

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