Three-dimensional (3D) printing technology has emerged, in the last few years, as an attractive option for regenerative medicine, owing to its promise of generating custom cell scaffolds, and potentially fabricate tissues, by placing cells in an environment – which is generally a growth medium – that supports their growth and proliferation. Once a technology mostly for printing mechanical constructs, 3D printing has crossed over into biomedicine.
Now, for the first time, a new study described the use of 3D printing technology to generate three-dimensional hydrogel scaffolds made of stem cells. Dr. Wei Sun and his lab at the Department of Mechanical Engineering at Drexel University authored the study that described using an extrusion-based 3D bioprinting approach developed in their lab. In microextrusion, structures are printed in 2D with hydrogel and the material is then made solid so the structures can be combined to create 3D shapes.
The authors printed embryonic stem cells into hydrogels in 3D grid-like patterns, shown in the image below.
The manuscript was published in Bioprinting.
The authors observed the cells to successfully proliferate into spheroid embryoid bodies in the hydrogel construct. The protein expression and expression of pluripotent genetic markers (OCT4, SSEA1, nanog and Antigen 1) was successfully observed.
The authors also postulate that the 3D hydrogel/ESC construct’s utility lies not only in its use as a potentially sophisticated 3D scaffold to study differentiation of ESCs in 3D environments, but also as a cell culture substrate, owing to its ability to generate large numbers of ESCs rapidly.
This week, Akron Biotechnology attended the annual CAR-T Summit, which took place in Boston, MA on November 12 and 13.
The Summit brought together experts from academia and industry who are at the forefront of advances that are helping understand and develop next-generation cures with CAR-T cell therapy.
Akron Biotechnology’s Dr. Claudia Zylberberg delivered a speech on the key aspects of raw material procurement for safe and compliant CAR-T therapies. The discussion focused on issues, from safety to economics, that drive the Cost of Goods of the final therapies and which are dictated by best practices at the raw material level. Four key raw material families were identified as key to CAR-T therapy development: human products, recombinant proteins, serum-free media and cryopreservation media. Akron’s presentation touched on best practices and cutting-edge science with respect to the procurement of these materials, as well as safety issues that would allow compliant manufacturing with particular regard to regulatory agencies.
Alongside Akron, Robert Margolin, VP of Corporate Development at Cognate Bioservices, our partner, presented on their capabilities as a leading service provider of autologous CAR-T manufacturing processes. Owing to Cognate’s location at the intersection of major carrier arteries (Cognate is located in the vicinity of Fedex’ main hub), Cognate’s capabilities are compounded by the ability to provide robust logistical solutions that result in rapid delivery of freshly manufactured therapies ready for bed-side administration. Cognate has a deep understanding of the requirements of the entire CAR-T therapy process – from regulatory aspects through to manufacturing, storage, scheduling, supply chain management and logistics, and their presentation reflected such experience.
Akron also participated as an exhibitor, where we presented the latest in our products, services and capabilities.
If you missed us or missed the meeting altogether but would like to discuss how we – or Cognate – can help, contact us directly.
CAR-T cell therapy, wherein T cells are engineered with chimeric antigen receptors (CARs) which enable them to “attack” cancer cells, has emerged as one of the most powerful and promising immunotherapy approaches in modern medicine.
A recent manuscript in Science, titled Remote control of therapeutic T cells through a small molecule–gated chimeric receptor, reported on a breakthrough approach for CAR-based therapy. Dr Wendel Lim and colleagues at the University of California San Francisco described the development of an “ON-switch” CAR–which is essentially a CAR whose activity is dependent on a small molecule.
In other words, the switch allows for external, remote control over CAR T cell activity by inducing such activity with the presence of a small molecule. This switch is reversible, so activity can be switched off just like it can be turned on.
The switch is based on small molecule-conjugated polypeptides.
While remarkable, this work is still at the proof of principle stage, but future development might include trigger and condition-specific switches which would allow the cells to further increase their specificity.
MEET AKRON AT CAR-T SUMMIT THIS WEEK
Akron will participate at the CAR-T Summit 2015 taking place November 12th and 13th in Boston, MA.
The summit brings together leaders in the field, from academia to industry, to tackle issues in clinical development, manufacturing and global commercialization of CAR-T therapies.
The Summit takes place at the Hyatt Regency in Cambridge.
To schedule a meeting, contact us.
Factors controlling the balance between stem cell renewal and differentiation have been the subject of several recent research papers. Just recently, exosomes were described as having a role in the induction of differentiation of human stem cells. Now, a new research paper claims to have identified a protein that is thought to be directly responsible for keeping a balance between differentiation and renewal
The study, titled “Coordination of m6A mRNA Methylation and Gene Transcription by ZFP217 Regulates Pluripotency and Reprogramming” was published this week in Cell Stem Cell by Dr Martin Walsh’s lab at the Icahn School of Medicine at Mount Sinai.
The authors identified a protein called “”zinc finger protein 217” as being responsible for the renewal-differentiation balance of human stem cells.
By using human embryonic stem cells, they discovered that ZFP217 activates the transcription of key pluripotency genes. It does so by modulating m6A deposition onto m6A methyltransferase-like 3 (METTL3) and rendering it inactive, which prevents methylations which causes the stem cells to differentiate, putting an end to their self-renewal and pluripotency.
The authors also discovered that ZFP217 turns on a number of genes important for stemness, including Nanog, Sox2, Klf4, and c-Myc.
Though preliminary, these important findings are adding to the deepening well of knowledge about the regulation of stem cell pluripotency, which have a potentially therapeutically tremendous impact in regenerative medicine.
The need for red blood cells for medical transfusions is a significant need that cannot be overstated. The cost of obtaining sufficient blood necessary for transfusions is often prohibitively high, and the difficulty in sourcing blood has, as a result, an unfortunate human cost.
Stem cells have, as a result, appeared as a way to generate RBCs for medical purposes where sourcing ready blood is not possible.
However, so far, the yield of red blood cells (RBCs) produced from stem cells in vitro has not shown to be practical for routine transfusion needs. The issues come down to scaling up red blood cell production to quantities useful for clinical trials, which has proven to be a significant challenge.
Finding ways in which red blood cell production from stem cells can be improved is an area of growing research interest. Now, a new study claims to have identified, via genetic engineering, a new way to significantly improve the yield of RBCs derived from stem cells.
The study, titled “Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells,” was published in Cell Stem Cell by Dr. Vijay Sankaran’s lab at the Dana-Farber Cancer Institute in collaboration with colleagues at Boston Children’s Hospital and the University of Pennsylvania.
The authors identified that silencing gene SH2B3 – which traditionally encodes a negative regulator of cytokine signaling – leads to an increase in RBC generation. By suppressing SH2B3 in primary human CD34+ hematopoietic stem and progenitor cells with SH2B3-targeting shRNAs, the authors demonstrated that the yield of in-vitro-derived RBCs three- to five-fold. In addition to that, this caused differentiation of stem cells to occur significantly more rapidly.
What this means practically, is that this technique could potentially improve RBC production at 80% less cost than traditional costs required to obtain equivalent amounts of RBCs.
The potential medical benefits are multi-fold, so it will be interesting to see further developments of this technology and whether further studies can support larger scale expansion.
We are closely monitoring this field, having recently published a manuscript to develop novel methodologies and cryopreservation solutions to freeze RBCs in ways that are safer for transfusion. Contact us to enquire.
We have previously, in this blog and public forums, drawn attention to the growing need for better standardization of cell therapies – from raw materials through to manufacturing and clinical administration.
Efforts on the part of various standardization bodies have increased in recent months, with a growing number of initiatives aimed at streamlining cell therapy processes.
While unlicenced stem cell clinics have been the subject of extensive write-ups in other media, and while the remit of standardization agencies does not necessarily cover these clinics, high-profile reports about these are worth paying attention to as they touch on the very real need for improved standardization efforts across the board.
A recent public call for the FDA to act upon these clinics was published recently in the New England Journal of Medicine. Drs. Hermes Taylor-Weiner and Joshua Graff Zivin called for the FDA to act upon unlicenced stem cell therapies by clarifying their position on legislation that is ambiguous.
A big point of contention, at least in the paper, appears to be administartion of stem cells from adipose (fat) tissue, which are collected by liposuction and called stromal vascular fraction (SVF). The degree of processing and manipulation is key here.
The FDA has recently issued draft guidance stating that SVF cells are likely to fall into a category of product that requires strict oversight and official approval for use in patients, adding that warning and guidelines will be issued to doctors administering such treatments.
Obtaining, processing and administering SVF stem cells touches on multiple steps in the cell therapy process – efforts at standardization cover every aspect of the stem cell therapy process.
Akron has been a proponent of standardization in the industry. We work with multiple industry bodies to try and streamline the steps involved in the cell therapy process and will continue to do so.
If you would like to talk to us about issues that involve standardization, traceability and process development, contact us.
How are stem cells affected by their surrounding?
This simple question is what Dr. Xin Chen, associate professor of biology at Johns Hopkins University’s Krieger School of Arts and Sciences has, alongside six co-authors from her lab, sought to answer in a new manuscript published this week in Cell Reports.
By studying the aminopeptidase Slamdance (Sda) acts in the Drosophila testicular niche, the authors discovered that sda acts to both maintain germline stem cells (GSCs) and regulate progenitor germ cell dedifferentiation.
Earlier, the authors had reported that the role of sda is significant in the niche: loss-of-function in sda leads to abnormalities in the testis niche, including deterioration of the niche architecture and loss of stem cells.
This makes it critical, as a niche-specific factor, for both germline and cyst stem cell maintenance.
However, questions arise about how the niche itself is regulated and, moreover, how this knowledge can be used to direct stem cell fate.
Ultimately, the authors do concede that further work is necessary to elucidate such mechanisms which might provide some clinical efficacy.
The full paper can be accessed here.