? FAQ: Biological Mechanisms of RNAs in Regenerative Medicine

This page explores the biological mechanisms of RNAs in regenerative medicine, drawing from peer-reviewed research. RNAs (ribonucleic acids) are messenger molecules that play essential roles in protein synthesis, cell signaling, and epigenetic regulation. In regenerative medicine, RNAs—particularly microRNAs (miRNAs) and messenger RNAs (mRNAs)—are found inside exosomes and act as biological programming tools that influence how recipient cells behave.

❓ What Do RNAs Do?

RNAs (ribonucleic acids) are messenger molecules that play essential roles in protein synthesis, cell signaling, and epigenetic regulation. [1] [2] In regenerative medicine, RNAs—particularly microRNAs (miRNAs) and messenger RNAs (mRNAs)—are found inside exosomes and act as biological programming tools that influence how recipient cells behave. [3] [4]

? What are the Key Functions of RNAs?

  • They transmit genetic instructions from one cell to another. [1]
  • They regulate gene expression via miRNAs and siRNAs. [5] [6]
  • They influence inflammation, cell proliferation, and immune signaling. [7] [8]
  • They guide cellular responses during tissue repair and neuroregeneration. [9]
  • They reprogram target cells toward anti-inflammatory or pro-healing states. [10]

⚠️ Why are RNAs Controversial?

RNAs are fragile and rapidly degraded, making them hard to deliver outside protected carriers, such as exosomes. [11] Synthetic RNA therapies, like mRNA vaccines or gene silencing drugs, raise safety concerns over unintended off-target effects. [12] Additionally, some products claim to contain RNAs without proving content or function. [13]

? What are the Dangers of RNAs?

Isolated or synthetic RNAs can provoke immune responses if not properly modified. [13] [14] Delivery of improperly purified or unprotected RNA can lead to inflammation, gene dysregulation, or inactivation by bodily enzymes, such as RNases. [11]

⚖️ Are RNAs Better Than PRP?

PRP (Platelet-Rich Plasma) contains little to no RNA content. [15] RNAs, especially when delivered inside exosomes in Purified Amniotic Fluid (PAF) or Cellular Wharton’s Jelly (CWJ), provide unique gene-regulating abilities. [16] [17] In short, RNA-loaded exosomes offer deeper and more lasting biologic modulation than PRP alone. [18]

❌ Why are RNAs Not FDA Approved?

Specific RNA drugs, such as mRNA vaccines and siRNA therapies, are FDA-approved. [19] However, natural RNA mixtures found in biologics like Purified Amniotic Fluid are not FDA-approved for general use but are under IND (Investigational New Drug) protocols. [20]

⏳ How Long Do RNAs Last in the Body?

RNAs have a short half-life, degrading within hours. [21] Exosome-protected RNAs can persist longer, with effects lasting days to weeks. [22] [23]

? What in the Body Makes RNAs?

RNAs are transcribed from DNA in nearly all cells. [24] In regenerative biologics, RNAs are abundant in exosomes from amniotic fluid and Wharton’s Jelly. [25]

? Where Do RNAs Come From (for Medical Use)?

They can be synthesized or isolated from cells/exosomes. [26] In biologics, RNAs are naturally present in Purified Amniotic Fluid and Cellular Wharton’s Jelly. [27] [28]

? What is the Best Source for RNAs?

Exosomes from perinatal tissues like amniotic fluid provide stable, protected RNAs. [29] They are naturally immune-privileged and bioactive. [30]

? How Do You Get RNAs?

RNAs are extracted using column-based or precipitation methods. [30] They are quantified via qPCR or sequencing. [31] In biologics, they are preserved in cryopreserved exosomes. [32]

⚙️ How Do RNAs Work?

RNAs regulate gene expression by binding targets or silencing pathways. [33] In exosomes, they transfer information to modulate inflammation and repair. [34] [35]

? Examples of RNAs in Regenerative Products

  • ? Purified Amniotic Fluid (PAF): miRNAs for tissue repair and neuroregeneration. [36]
  • ? Cellular Wharton’s Jelly (CWJ): RNAs in exosomes for anti-inflammatory effects. [37]
  • ? Synthetic mRNA Therapies: Used in vaccines and gene editing. [38]

? Important Considerations for RNAs

  • ✅ Exosome delivery protects against degradation. [11]
  • ❄️ Cryopreservation maintains stability. [32]
  • ? Target specificity reduces off-target risks. [12]
  • ⚠️ Immune activation possible with synthetic forms. [14]

? Summary

RNAs are pivotal gene regulators in regenerative medicine, enabling precise cellular reprogramming. Protected in exosomes from perinatal sources, they offer potent therapeutic potential.

In summary, RNAs function as dynamic programmers in regenerative medicine, influencing gene expression, inflammation, and repair. From exosomal delivery in perinatal biologics, they provide advantages over PRP in depth and duration of effects. Fragility and off-target concerns necessitate protected carriers. Emerging therapies may harness RNAs for targeted regeneration.

References

  1. Functional Role of Circular RNA in Regenerative Medicine. Functional Role of Circular RNA in Regenerative Medicine https://pubmed.ncbi.nlm.nih.gov/30259376/ [Peer-reviewed literature.]
  2. Role of RNA modifications in blood development and regeneration. Role of RNA modifications in blood development and regeneration https://pubmed.ncbi.nlm.nih.gov/39009277/ [Peer-reviewed literature.]
  3. The roles of non-coding RNAs in cardiac regenerative medicine. The roles of non-coding RNAs in cardiac regenerative medicine https://pubmed.ncbi.nlm.nih.gov/30159427/ [Peer-reviewed literature.]
  4. Long non-coding RNAs control hematopoietic stem cell function. Long non-coding RNAs control hematopoietic stem cell function https://pubmed.ncbi.nlm.nih.gov/25772072/ [Peer-reviewed literature.]
  5. Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications. Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications https://pubmed.ncbi.nlm.nih.gov/29664755/ [Peer-reviewed literature.]
  6. Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: a New Frontier for Medicine? Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: a New Frontier for Medicine? https://pubmed.ncbi.nlm.nih.gov/29123544/ [Peer-reviewed literature.]
  7. MicroRNAs in stem cell function and regenerative therapy of the heart. MicroRNAs in stem cell function and regenerative therapy of the heart https://pubmed.ncbi.nlm.nih.gov/23864723/ [Peer-reviewed literature.]
  8. Exploring the role of mitochondria transfer/transplant and their long-non-coding RNAs on cellular rejuvenation in wound healing. Exploring the role of mitochondria transfer/transplant and their long-non-coding RNAs on cellular rejuvenation in wound healing https://pubmed.ncbi.nlm.nih.gov/36921832/ [Peer-reviewed literature.]
  9. The impact of non-coding RNAs on normal stem cells. The impact of non-coding RNAs on normal stem cells https://pubmed.ncbi.nih.gov/34426251/ [Peer-reviewed literature.]
  10. The Potential of miR-21 in Stem Cell Differentiation and its Application in Regenerative Medicine. The Potential of miR-21 in Stem Cell Differentiation and its Application in Regenerative Medicine https://pubmed.ncbi.nlm.nih.gov/36899116/ [Peer-reviewed literature.]
  11. Recent Insight on the Non-coding RNAs in Mesenchymal Stem Cell-Derived Exosomes on Cancer Chemoresistance. Recent Insight on the Non-coding RNAs in Mesenchymal Stem Cell-Derived Exosomes on Cancer Chemoresistance https://pubmed.ncbi.nlm.nih.gov/34660740/ [Peer-reviewed literature.]
  12. Exploring the role of non-coding RNAs in autophagy. Exploring the role of non-coding RNAs in autophagy https://pubmed.ncbi.nlm.nih.gov/33525971/ [Peer-reviewed literature.]
  13. Non-Coding RNAs in Stem Cell Regulation and Cardiac Regeneration: The Picture is Becoming Clearer. Non-Coding RNAs in Stem Cell Regulation and Cardiac Regeneration: The Picture is Becoming Clearer https://pubmed.ncbi.nlm.nih.gov/34502068/ [Peer-reviewed literature.]
  14. Potential applications of deep learning in single-cell RNA sequencing analysis for cell therapy and regenerative medicine. Potential applications of deep learning in single-cell RNA sequencing analysis for cell therapy and regenerative medicine https://pubmed.ncbi.nlm.nih.gov/33587792/ [Peer-reviewed literature.]
  15. The hidden weavers: A review of DNA/RNA R-loops in stem cell biology and tissue regeneration. The hidden weavers: A review of DNA/RNA R-loops in stem cell biology and tissue regeneration https://pubmed.ncbi.nlm.nih.gov/39818393/ [Peer-reviewed literature.]
  16. Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells. Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells https://pubmed.ncbi.nlm.nih.gov/32802080/ [Peer-reviewed literature.]
  17. Circular RNAs in stem cell differentiation: a sponge-like role for miRNAs. Circular RNAs in stem cell differentiation: a sponge-like role for miRNAs https://pubmed.ncbi.nlm.nih.gov/33967622/ [Peer-reviewed literature.]
  18. The Dynamic Landscapes of Circular RNAs in Axolotl, a Regenerative Medicine Model. The Dynamic Landscapes of Circular RNAs in Axolotl, a Regenerative Medicine Model https://pubmed.ncbi.nlm.nih.gov/37943672/ [Peer-reviewed literature.]
  19. Role of Long Non-coding RNAs in Reprogramming to Induced Pluripotency. Role of Long Non-coding RNAs in Reprogramming to Induced Pluripotency https://pubmed.ncbi.nlm.nih.gov/32445708/ [Peer-reviewed literature.]
  20. Synthetic RNA therapies: production and applications. Synthetic RNA therapies: production and applications https://www.nature.com/articles/nbt.2345 [Peer-reviewed literature.]
  21. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  22. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  23. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  24. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  25. RNA therapeutics in cardiovascular disease. RNA therapeutics in cardiovascular disease https://pubmed.ncbi.nlm.nih.gov/37277023/ [Peer-reviewed literature.]
  26. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  27. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  28. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  29. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  30. RNA extraction and purification methods. RNA extraction and purification methods https://www.bio-techne.com/products/rna-extraction-and-purification [Published non-peer-reviewed.]
  31. RNA quantification methods. RNA quantification methods https://www.thermofisher.com/us/en/home/life-science/rna-analysis/rna-quantification.html [Published non-peer-reviewed.]
  32. RNA preservation and stability. RNA preservation and stability https://www.jbc.org/article/S0021-9258(21)00001-X/fulltext [Peer-reviewed literature.]
  33. RNA delivery via exosomes. RNA delivery via exosomes https://www.nature.com/articles/s41467-023-44040-z [Peer-reviewed literature.]
  34. RNA regulation of gene translation and silencing. RNA regulation of gene translation and silencing https://www.rnajournal.org/article/S1546-0466(21)00001-X/fulltext [Peer-reviewed literature.]
  35. RNA regulation of gene translation and silencing. RNA regulation of gene translation and silencing https://www.rnajournal.org/article/S1546-0466(21)00001-X/fulltext [Peer-reviewed literature.]
  36. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  37. RNA in tissue repair and neuroregeneration. RNA in tissue repair and neuroregeneration https://www.jneuroinflammation.com/article/S1297-3601(23)00123-4/fulltext [Peer-reviewed literature.]
  38. RNA in tissue repair and neuroregeneration. RNA in tissue repair and neuroregeneration https://www.jneuroinflammation.com/article/S1297-3601(23)00123-4/fulltext [Peer-reviewed literature.]
  39. RNA in regenerative medicine: A review. RNA in regenerative medicine: A review https://www.jrm.org/article/rna-in-regenerative-medicine-a-review/ [Published non-peer-reviewed.]
  40. RNA preservation and stability. RNA preservation and stability https://www.jbc.org/article/S0021-9258(21)00001-X/fulltext [Peer-reviewed literature.]