A scalable xeno-free microcarrier suspension bioreactor system for regenerative medicine biomanufacturing of hMSCs

An economical biomanufacturing paradigm for human mesenchymal stem/stromal cells (hMSCs) is in critical need, as indicated by over 800 clinical trials investigating the use of hMSCs for regenerative medicine. To meet the demand for clinical manufacturing, a scalable process and production technology platform that can generate billions to trillions of cells per manufacturing lot is needed. Suspension bioreactors show great promise in reaching commercially-viable working volumes, however, scalability of cell production remains an issue. Overcoming this challenge is necessary to drive widespread adoption of this culture system for hMSCs. We have taken the Quality by Design (QbD) approach to develop a scalable xeno-free (XF) hMSC bioreactor process that maintains the final cell population doubling level (PDL) within the recommended range of 16-20 to ensure product quality. Our strategic XF bioprocess was designed using high volume XF cell banks, an optimized XF fed-batch media system, and XF microcarriers, all combined in a scalable bioreactor system to meet our design criteria and streamlined production at different culture scales. Please click Additional Files below to see the full abstract

Regen med therapeutic opportunities for fighting COVID-19.

This perspective from a Regenerative Medicine Manufacturing Society working group highlights regenerative medicine therapeutic opportunities for fighting COVID-19. This article addresses why SARS-CoV-2 is so different from other viruses and how regenerative medicine is poised to deliver new therapeutic opportunities to battle COVID-19. We describe animal models that depict the mechanism of action for COVID-19 and that may help identify new treatments. Additionally, organoid platforms that can recapitulate some of the physiological properties of human organ systems, such as the lungs and the heart, are discussed as potential platforms that may prove useful in rapidly screening new drugs and identifying at-risk patients. This article critically evaluates some of the promising regenerative medicine-based therapies for treating COVID-19 and presents some of the collective technologies and resources that the scientific community currently has available to confront this pandemic

A novel single-step self-assembly approach for the fabrication of tissue-engineered vascular constructs

There is a clinical need for a functional tissue-engineered blood vessel because small-caliber arterial graft (<5 mm) applications are limited by the availability of suitable autologous vessels and suboptimal performances of synthetic grafts. This study presents an analysis of the mechanical properties of tissue-engineered vascular constructs produced using a novel single-step self-assembly approach. Briefly, the tissue-engineered vascular media were produced by culturing smooth muscle cell in the presence of sodium l-ascorbate until the formation of a cohesive tissue sheet. This sheet was then rolled around a tubular support to create a media construct. Alternatively, the tissue-engineered vascular adventitia was produced by rolling a tissue sheet obtained from dermal fibroblasts or saphenous vein fibroblasts. The standard self-assembly approach to obtain the two-layer tissue-engineered vascular constructs comprising both media and adventitia constructs consists of two steps in which tissue-engineered vascular media were first rolled on a tubular support and a tissue-engineered vascular adventitia was then rolled on top of the first layer. This study reports an original alternative method for assembling tissue-engineered vascular constructs comprising both media and an adventitia in a single step by rolling a continuous tissue sheet containing both cell types contiguously. This tissue sheet was produced by growing smooth muscle cells alongside fibroblasts (saphenous vein fibroblasts or dermal fibroblasts) in the same culture dish separated by a spacer, which is removed later in the culture period. The mechanical strength assessed by uniaxial tensile testing, burst pressure measurements, and viscoelastic behavior evaluated by stepwise stress relaxation tests reveals that the new single-step fabrication method significantly improves the mechanical properties of tissue-engineered vascular construct for both ultimate tensile strength and all the viscoelastic moduli

Highlights on Advancing Frontiers in Tissue Engineering

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