Tentacle patterning during Exaiptasia diaphana pedal lacerate development differs between symbiotic and aposymbiotic animals

Exaiptasia diaphana, a tropical sea anemone known as Aiptasia, is a tractable model system for studying the cellular, physiological, and ecological characteristics of cnidarian-dinoflagellate symbiosis. Aiptasia is widely used as a proxy for coral-algal symbiosis, since both Aiptasia and corals form a symbiosis with members of the family Symbiodiniaceae. Laboratory strains of Aiptasia can be maintained in both the symbiotic (Sym) and aposymbiotic (Apo, without algae) states. Apo Aiptasia allow for the study of the influence of symbiosis on different biological processes and how different environmental conditions impact symbiosis. A key feature of Aiptasia is the ease of propagating both Sym and Apo individuals in the laboratory through a process called pedal laceration. In this form of asexual reproduction, small pieces of tissue rip away from the pedal disc of a polyp, then these lacerates eventually develop tentacles and grow into new polyps. While pedal laceration has been described in the past, details of how tentacles are formed or how symbiotic and nutritional state influence this process are lacking. Here we describe the stages of development in both Sym and Apo pedal lacerates. Our results show that Apo lacerates develop tentacles earlier than Sym lacerates, while over the course of 20 days, Sym lacerates end up with a greater number of tentacles. We describe both tentacle and mesentery patterning during lacerate development and show that they form through a single pattern in early stages regardless of symbiotic state. In later stages of development, Apo lacerate tentacles and mesenteries progress through a single pattern, while variable patterns were observed in Sym lacerates. We discuss how Aiptasia lacerate mesentery and tentacle patterning differs from oral disc regeneration and how these patterning events compare to postembryonic development in Nematostella vectensis, another widely-used sea anemone model. In addition, we demonstrate that Apo lacerates supplemented with a putative nutrient source developed an intermediate number of tentacles between un-fed Apo and Sym lacerates. Based on these observations, we hypothesize that pedal lacerates progress through two different, putatively nutrient-dependent phases of development. In the early phase, the lacerate, regardless of symbiotic state, preferentially uses or relies on nutrients carried over from the adult polyp. These resources are sufficient for lacerates to develop into a functional polyp. In the late phase of development, continued growth and tentacle formation is supported by nutrients obtained from either symbionts and/or the environment through heterotrophic feeding. Finally, we advocate for the implementation of pedal lacerates as an additional resource in the Aiptasia model system toolkit for studies of cnidarian-dinoflagellate symbiosis.

Matrilin3/TGFβ3 gelatin microparticles promote chondrogenesis, prevent hypertrophy, and induce paracrine release in MSC spheroid for disc regeneration

Degenerative disc disease (DDD) is the leading cause of excruciating lower back pain and disability in adults worldwide. Among the current treatments for DDD, cell-based therapies such as the injection of both disc- and non-disc-derived chondrocytes have shown significant improvements in the patients’ condition. However, further advancement of these therapies is required to not only ensure a supply of healthy chondrocytes but also to promote regeneration of the defective cells in the injury site. Here, we report that the incorporation of gelatin microparticles coloaded with transforming growth factor beta 3 and matrilin 3 promoted chondrogenic differentiation of adipose-derived mesenchymal stem cell spheroids while preventing hypertrophy and terminal differentiation of cells. Moreover, these composite spheroids induced the release of chondrogenic cytokines that, in turn, promoted regeneration of degenerative chondrocytes in vitro. Finally, injections of these composite spheroids in a rat model of intervertebral disc disease promoted restoration of the chondrogenic properties of the cells, thereby allowing regeneration of the chondrogenic tissue in vivo.

Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc

Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.

Intervertebral Disc Stem/Progenitor Cells: A Promising “Seed” for Intervertebral Disc Regeneration

Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain (LBP), which has become more prevalent from 21 century, causing an enormous economic burden for society. However, in spite of remarkable improvements in the basic research of IVD degeneration (IVDD), the effects of clinical treatments of IVDD are still leaving much to be desired. Accumulating evidence has proposed the existence of endogenous stem/progenitor cells in the IVD that possess the ability of proliferation and differentiation. However, few studies have reported the biological properties and potential application of IVD progenitor cells in detail. Even so, these stem/progenitor cells have been consumed as a promising cell source for the regeneration of damaged IVD. In this review, we will first introduce IVD, describe its physiology and stem/progenitor cell niche, and characterize IVDSPCs between homeostasis and IVD degeneration. We will then summarize recent studies on endogenous IVDSPC-based IVD regeneration and exogenous cell-based therapy for IVDD. Finally, we will discuss the potential applications and future developments of IVDSPC-based repair of IVD degeneration.

Critical genetic program for Drosophila imaginal disc regeneration revealed by single-cell analysis

Whether regeneration is primarily accomplished by re-activating gene regulatory networks used previously during development or by activating novel regeneration-specific transcriptional programs remains a longstanding question. Currently, most genes implicated in regeneration also function during development. Using single-cell transcriptomics in regenerating Drosophila wing discs, we identified two regeneration-specific cell populations within the blastema. They are each composed of cells that upregulate multiple genes encoding secreted proteins that promote regeneration. In this regenerative secretory zone, the transcription factor Ets21C controls the expression of multiple regeneration-promoting genes. While eliminating Ets21C function has no discernible effect on development, it severely compromises regeneration. This Ets21C-dependent gene regulatory network is also activated in blastema-like cells in tumorous discs, suggesting that pro-regenerative mechanisms can be co-opted by tumors to promote aberrant growth.