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| Aspect | Stem cell | Secretome |
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| Manufacturing | (i) General culture condition is normally used but special culture condition might be needed to produce specific cells (e.g., chondrogenic media to produce chondrogenic-differentiated MSCs)
(ii) The consistency of the cell source has to be maintained for allogeneic stem cells
(iii) May contain elements of external sources (FBS, HPL)
(iv) Require a large number of cells for clinical applications | (i) General culture condition can be used but special culture condition mimicking the pathophysiological condition of the target diseases might be needed to produce the “bioequivalent” secretome
(ii) The consistency of the cell source has to be maintained
(iii) Enrichment protocol might be needed to enhance the production of secretome
(i) Secretome may contain elements of external sources (FBS, HPL)
(ii) High volume of media is collected, and it needs to be processed and concentrated for clinical applications |
| Quality control | (i) Stem cell markers are well established
(ii) The characterization techniques are well established
(iii) Specific functionality assay is needed to determine the efficacy | (i) The characterization is complex since secretome contain many elements such as growth factors, cytokines, and extracellular vesicles
(ii) Specific functionality assay is needed to determine its efficacy |
| Cost of production and treatment | (i) Cost can be reduced via large-scale expansion of allogeneic stem cells
(ii) Treatment dose is easier to be justified by number of cells | (i) Repetitive collection of secretome from spent culture media can greatly reduce the cost of production
(ii) Extra cost is needed for downstream processing of secretome (concentration and purification)
(iii) Treatment dose is vague (protein amount vs number of particles)
(iv) It is unsure which component(s) of the secretome are exerting therapeutic effects |
| Advantages | (i) Stem cells can be differentiated into specific lineages to improve the therapeutic efficacy and treat different diseases
(ii) Mesenchymal stem cells are easy to isolate and expand, have low immunogenicity (both autologous and allogeneic cells can be used clinically), free from ethical issues, and have limited replicative lifespan, hence safe from malignant formation
(iii) Can be reprogrammed into pluripotent stem cells (PSCs)
(iv) Can cross blood-brain barrier (BBB)
(v) Can migrate and home to the target tissue in response to the signal release by the injured cells
(vi) Living cells can exert the therapeutic effects for a longer period. Thus, less frequency of administration is needed (e.g., once in every 6 months) | (i) The therapeutic components of the secretome could be customized by modifying the culture condition (preconditioning)
(ii) Can cross BBB
(iii) Can circulate and home to the target tissue
(iv) Low risk of mutation, carcinogenesis, and immunogenic as they are not living cells
(v) Lower risk of vascular obstruction as they are smaller in size compared to stem cells
(vi) Easier to store
(vii) Cell degeneration or senescence in the host after transplantation is not a concern |
| Disadvantages | (i) Higher risk of mutation and carcinogenesis (especially the PSCs)
(ii) Ethical issue (embryonic stem cells)
(iii) Might illicit host immune response to reject the transplanted cells (especially the allogeneic stem cells)
(iv) Cell degeneration or senescence in the host after transplantation
(v) Potential vascular obstruction
(vi) More stringent storage condition to maintain the cell viability
(vii) More optimization is needed to improve the safety and efficacy (e.g., optimum dosage and route of administration) | (i) Cannot be used as cell-replacement therapy and relying on the proliferation of host cells for tissue regeneration
(ii) Lack of understanding on its mechanism of action
(iii) Lack of long-term safety data
(iv) Lack of standardization
(v) Short half-life in the body. Thus, might need more frequent administration
(vi) Difficult to purify the specific therapeutic components (e.g., exosomes). Thus, the secretome products are highly heterogeneous |
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