Introduction /               

With the advancement of science and technology, drugs are also evolving and evolving. Early on, drugs mainly pursued symptom control and reduction of patients' pain, but nowadays, the general direction has shifted to curing the disease from the root. Regenerative medicine, which replaces or repairs damaged cells and tissues, is undoubtedly a big hit in this direction.

1. Cell therapy

Research related to cell therapy has been very active in recent years, and according to the Clinical Trials Database (clinicaltrials.gov), there have been 1,133 clinical studies on mesenchymal stem cells alone in recent years. These clinical studies are broadly categorised into two types: autologous and allogeneic cell therapy.

 

Figure 1: Sourced from literature [1]

 

Both autologous and allogeneic cell therapy involve culturing cells in vitro for several cycles, obtaining a large number of cells and then infusing them back into the patient, with the difference being that in autologous cell therapy the cells are harvested from the patient, cultured, and then re-infused back into that patient, while in allogeneic cell therapy the source of the cells is the donor, and the re-infusion is done to recipients other than the donor.

The allogeneic source makes the mass production of MSCs possible, greatly reducing the cost of production, and no longer corresponds to the individual also makes the idea of research broader, more valuable research. Therefore, allogeneic stem cell therapy is promising to become a new generation of therapeutic drugs, but it still faces some challenges.

 

2、Cell thin section technology

In most clinical applications, stem cell therapy relies on in vitro culture, cell separation into suspension, and then intravenous injection of mesenchymal stem cells into the body (Fig. 2.A). This approach can achieve certain therapeutic effects, but there are some limitations: ① there is no purpose, and it is not possible to focus on targeting a specific tissue or organ; ② the therapeutic effects vary depending on the patient's individual physique.

In order to solve these problems, T. Okano pioneered the cell sheet technology, in which cells are cultured in vitro in special dishes and harvested in the form of cell sheets by changing the temperature, and the harvested cell sheets enable the cells to be delivered efficiently to the target tissues or organs (Fig. 2.B).

 

Figure 2: Sourced from literature [1]

 

3. New research: Cell sheet technology regenerates organ tissue

Since its invention, this technique has spawned research in several human disease indications. In an article published in the Journal of Controlled Release, Volume 330, "Allogeneic mesenchymal stem cell sheet therapy: A new frontier in Allogeneic mesenchymal stem cell sheet therapy: A new frontier in drug delivery systems," published in the Journal of Controlled Release, Volume 330, researchers have used this technology to achieve results in tissue regeneration therapy in animal models.

 

Figure 3: Sourced from literature [1]Sciencedirect(www.sciencedirect.com)

The researcher obtained MSCs, cultured them in vitro with TRCD to obtain thin slices of stem cells, and transplanted them into the relevant organs. The gradual thickening of the MSC tissue led to the regeneration of the organ tissues, resulting in the gradual restoration of the damaged organs to their original state, and achieving good therapeutic effects.

Figure 4: Sourced from literature [1]

 

4. Heart regeneration by cell sheet technology

The researcher used adipose stem cells isolated from rats and cultured on TRCD to obtain lamellar mesenchymal stem cell sheets, which were then transplanted into scarred myocardium caused by myocardial atrophy. The transplanted cell sheets secreted large amounts of vascular endothelial cell growth factor, which promoted blood vessel growth and tissue regeneration, increased the quality of the thinned heart wall, improved the related symptoms, and provided a good therapeutic effect.

 

Figure 5: Sourced from literature [1]

 

5. Cell sheet technology regenerates kidneys

The researcher used bone marrow mesenchymal stem cells extracted from rats, and made good progress in treating the rat kidney ischaemia-reperfusion model: the researcher transplanted thin slices of bone marrow mesenchymal stem cells directly onto the surface of kidneys, and the results showed that the transplanted cell thin slices promoted the regeneration of microvessels in kidneys, and inhibited the overall renal dysfunction. This suggests that cell sheets applied to kidney regeneration also provide good therapeutic results.

 

Figure 6: Sourced from literature [1]

 

6. Summary

Overall, the cell sheet technique has been able to accurately target tissues in animal models with good therapeutic efficacy. With the publication of this result, more research teams will devote themselves to human clinical trials, and it is worthwhile to wait for the results of the next human clinical trials. Hopefully, one day, this result will revolutionise our lives and make repairing organ damage as easy and convenient as applying a band-aid.

From the great popularity of CAR-T cell therapy in recent years, it is not difficult to see that pharmaceutics is currently moving towards the use of living cells and tissues, and this breakthrough will likely give rise to new research directions that will promote cell therapy as the next generation of drugs.

A number of regenerative medicine treatments are already in the clinical stage.

In the future, the field of gene and cell therapy has broad prospects for development.