The thyroid is a tiny organ, but it can cause some big problems if it malfunctions – and there are quite a few ways in which it can malfunction. It’s also especially problematic because while other organ problems can be corrected through transplantation, thyroid transplants aren’t done – the risks of rejection and problems caused by immunosuppression are considered to far outweigh the benefits compared to treatment with drugs. That may change soon, though. The reason scientists are so eager to create 3D printed, transplantable organs is not only because organs can be created on demand, rather than waiting for a donor – it’s also because organs created from a patient’s own stem cells carry much less risk of rejection.

In 2015, a group of scientists at Russian company 3D Bioprinting Solutions made history when they successfully 3D printed and transplanted a thyroid gland into a mouse. We’ve now received an update on the scientists’ research, which has been published in a paper entitled “Bioprinting of functional vascularized mouse thyroid gland construct,” available here.

Despite the complex problems it can cause, the thyroid gland is a fairly simple structure, making it an easy candidate for 3D printing.

“We selected thyroid gland for proof of concept as anatomically relatively simple organ,” Dr. Vladimir Mironov, Chief Scientific Officer at 3D Bioprinting Solutions, tells 3DPrint.com. “Thyroid gland is an endocrine organ and it does not have complex ductal systems. Thyroid gland basically consists of thyroid follicles and vascular system.”

The researchers utilized a scaffold-free 3D printing technique using tissue spheroids, which are capable of fusing on their own. Thyroid spheroids (TS) and allantoic spheroids (AS) were used as sources for thyrocytes and endothelial cells (EC), and a custom bioprinter was used to print the spheroids in tight formation within a collagen hydrogel. The endothelial cells, placed in close proximity to the thyroid spheroids, invaded and vascularized them, while the epithelial cells from the thyroid spheroids formed follicles.

“In this experimental setting, we observed formation of capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles,” the researchers state. “To prove that EC from AS are responsible for vascularization of thyroid gland construct, we depleted endogenous EC from thyroid spheroids before bioprinting. EC from allantoic spheroids completely revascularized depleted thyroid tissue. Cultured bioprinted construct was functional as it could normalize blood thyroxin levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents further advance in bioprinting technology exploring self-assembling properties of tissue spheroids.”

The bioprinter used for the process, called Fabion, was specially developed in-house and consists of several functional parts including a syringe pump, a fluidic chip, a loading piston, a trapping piston, and a depositing piston with a groove for liquid removal. The systems work together to enable extreme precision when 3D printing; a single tissue spheroid can be deposited at a time. The bioprinter also includes a heating and cooling system to allow for better control over the polymerization of the collagen hydrogel, in which the 3D printed thyroid constructs were then cultured for four days.

The 3D printed thyroids were then transplanted into mice with hypothyroidism. After three and five weeks, the mice were tested and showed significant elevation of critical thyroid hormone levels, indicating that the bioprinted organ constructs were indeed doing the work they had been designed to do. Histological evaluation also showed that the bioprinted thyroids were able to successfully mature and integrate with the rest of the body.

According to Dr. Mironov, the researchers plan to 3D print a human thyroid gland in 2018, and also to work with the University of Oulu to bioprint a mini-kidney using kidney organoids.

“Our approach will allow to bioprint eventually any human organ,” he tells us.

The paper has received significant support from experts in the field, highlighting its relevance and the applicability of this research to future developments.

“Although the authors used dissected and rounded embryonic tissue spheroids and printed mouse cells, and not human thyroid gland, this paper has great value because it demonstrates the feasibility of organ printing using tissue spheroid as building blocks,” wrote Utkan Demirci, Ph.D., Associate Professor, Radiology; Associate Professor (By courtesy), Electrical Engineering, Stanford University.

“Dr. Mironov’s paper demonstrates a successful bioprinting of functional and vascularized organ-like construct. It is my opinion that this paper will represent an important milestone in the development of 3D bioprinting technology in the rapidly evolving field of 21st century biomedical science and technology.”

In another letter of support, Professor Chee Kai Chua, the Executive Director of Singapore Centre for 3D Printing, wrote:

“I support this manuscript because of its unprecedented significance. In this manuscript, the world’s first man-made near-organ living construct is reported, which represents a true breakthrough since the invention of tissue engineering by Dr Robert Langer in 1993. For the first time on Earth, a vascularised functional organ of a living organism has been 3D bioprinted. This small step on a mouse’s thyroid gland fills the future of human life with endless hopes and unimaginable possibilities.”

Authors of the paper include Elena A. Bulanova, Elizaveta V. Koudan, Jonathan Degosserie, Charlotte Heymans, Frederico D.A.S. Pereira, Vladislav A. Parfenov, Yi Sun, Qi Wang, Suraya A. Akhmedova, Irina K. Sviridova, Natalia S. Sergeeva, Georgy A. Frank, Yusef D. Khesuani, Christophe E. Pierreux, and Vladimir A. Mironov. Discuss in the 3D Printed Thyroid forum at 3DPB.com.

 

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