Humans have 23 intervertebral discs (IVD), whose thickness accounts for about 1/4 of the full length of the spine above the sacrum
"Intervertebral disc degenerative disease is a general term for a large group of diseases related to intervertebral disc degeneration, including cervical spondylosis, lumbar disc herniation, lumbar spinal stenosis, etc.
"Our research strategy is to obtain 100,000 cells from healthy intervertebral discs, sequence them one by one, and then integrate them for bioinformatics analysis.
Liu Peng believes that more importantly, this research has identified a new group of nucleus pulposus progenitor cells (NPPC) from the transcriptome and functional level.
Liu Peng and Liu Bing are the co-corresponding authors of the study.
Academy of Sciences The first step of "treating the symptoms": drawing a single cell map of human intervertebral discs
The first step of "treating the symptoms": drawing a single cell map of human intervertebral discs In the past research, scientists have continuously explored the physiology and pathology of the intervertebral disc, seeking innovative treatment methods to rebuild the homeostasis of the intervertebral disc
"The intervertebral disc is the most critical structure connecting the vertebral bodies.
The existing treatment methods are mainly divided into conservative treatment and surgical treatment
"In general, the clinical effects of the current treatment methods are satisfactory.
In fact, previous studies have found that there are many different types of cellular components in human intervertebral discs
In the latest study by Liu Peng et al.
The research team identified the following main cell subgroups through integrated analysis: three subgroups of chondrocytes, chordal cells, stromal cells, pericytes, endothelial cells, nucleus pulposus progenitor cells, blood cells, osteoblasts and a small number of nerve cells
Subsequently, the researchers also reclassified the three groups of chondrocytes based on the characteristics of the extracellular matrix (ECM) homeostasis, and further identified them as regulated, steady-state and effector types
Studies believe that the differences in the characteristics of these chondrocyte subgroups in the extracellular matrix provide a new perspective for further exploring the mechanism by which chondrocytes maintain the homeostasis of the intervertebral disc
The study also found that the nucleus pulposus progenitor cell subgroup specifically expressed the mesenchymal progenitor cell marker PDGFRA and the mesoderm-derived mesenchymal marker PRRX1, suggesting that there may be a cell population with stemness potential in the nucleus pulposus
Subsequently, the researchers used PROCR enrichment and sorted the nucleus pulposus progenitor cell population, and found that the cell population has a strong ability to form clones in vitro
.
Finally, consistent with the pseudo-chronological analysis, in vitro experiments confirmed that PROCR+ cells have the ability to differentiate into three lines of osteogenic, cartilage and adipogenesis
.
Liu Peng said, "The original intention of our research is to study the cellular structure and cellular microenvironment of the intervertebral disc using the most basic structure of the human body, that is, the cell scale
.
"
He concluded that in general, their study found that there are a variety of chondrocytes with different functions in the intervertebral disc, and they have made a new classification according to their functions; more importantly, they have discovered a new type of nucleus pulposus progenitor cells, This type of cell is proven to have the characteristics of stem cells and has the potential to regenerate
.
"Our research is the first systematic study of human intervertebral discs at the single-cell level in the world
.
It is of great significance for humans to understand intervertebral discs and treat degenerative disc diseases .
" Research pattern diagram
.
Reverse degeneration and regenerate an intervertebral disc?
Reverse degeneration and regenerate an intervertebral disc? It is worth noting that the current field of intervertebral disc research mainly focuses on two general directions: one is the study of the pathological mechanism of intervertebral disc degeneration, and the other is the study of treatment strategies
.
Liu Peng et al.
’s research does not belong to these two popular directions, but they believe that “it has important enlightenment for these two popular directions
.
” He believes that the study of the cellular composition and cell microstructure of the intervertebral disc in the physiological state Environmental composition is to analyze the basic composition and function of the intervertebral disc from the bottom
.
This single-cell atlas may provide an important treasure trove of clues for understanding the pathological changes of intervertebral discs and treating degenerative disc diseases
.
As far as Liu Peng's group is concerned, they have always dreamed of using organoid construction to try to solve degenerative disc disease
.
Generally speaking, the spine begins to degenerate from the age of 20-25
.
Of course, we usually do not see frequent back pain in young people, and the intervertebral discs require a longer wear and tear time
.
In addition, normal aging is not the only cause of intervertebral disc degeneration, other reasons can also cause it
.
"As we all know, the use of tissue engineering technology can already create an artificial, live nose or ear for organ defect repair and plastic surgery
.
We hope to use similar methods to replace the diseased intervertebral disc, or use biology Technology to reverse the degeneration of the intervertebral disc
.
" Liu Peng called it "intervertebral disc regenerative medicine
.
"
However, the long-standing debate is, what kind of cells can regenerate an intervertebral disc? "We have always believed that the most potential cells are inside the intervertebral disc
.
"
Liu Peng emphasized that this study also initially verified their conjecture, “a group of rare cells have been discovered, which have some stem cell marker genes, which we call nucleus pulposus progenitor cells
.
The nucleus pulposus cells not only have good cloning The ability to differentiate into bone and chondrocytes
.
Further analysis using bioinformatics technology found that platelet growth factor and transforming growth factor have the effect of promoting the proliferation of nucleus pulposus progenitor cells and the formation of cartilage
.
"
Liu Peng believes that all these results suggest that the rational use of cytokines is expected to use nucleus pulposus progenitor cells to achieve the regeneration and repair of the nucleus pulposus of the intervertebral disc
.
In these previous studies, Liu Peng and others established a single-cell transcriptome database of healthy intervertebral discs, but this information is still only the tip of the iceberg
.
"We are now sharing this database with our colleagues all over the world, hoping to work together with our colleagues to deeply understand the cell composition, function and intercellular interaction of the intervertebral disc, and to explore the biological treatment strategies and methods of degenerative disc diseases
.
"
Ultimately, they hope that they can “cure the root cause” on the basis of the existing “temporary cure”
.
Link to the paper: https://
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