? FAQ: Biological Mechanisms of Therapeutic Cell Markers (CD73⁺, CD90⁺, CD31⁺, CD45–) in Regenerative Medicine

This page explores the biological mechanisms of therapeutic cell markers, such as CD73, CD90, CD31, and CD45, in regenerative medicine, drawing from peer-reviewed research. These markers are surface proteins used to identify and characterize different types of cells, particularly those used in regenerative therapies. When a cell expresses or lacks these markers, it reveals its biological identity, function, and therapeutic relevance.

❓ What Do These Cell Markers Indicate?

These markers are surface proteins used to identify and characterize different types of cells, particularly those used in regenerative therapies. [1] [2] When a cell expresses or lacks these markers, it reveals its biological identity, function, and therapeutic relevance. [3] [4]

? What Do Each of These Markers Mean?

? CD73⁺ and CD90⁺

  • These are markers of Mesenchymal Signaling Cells (MSCs). [5]
  • They are associated with anti-inflammatory and immunomodulatory properties. [6] [7]
  • They are key identifiers in FDA and ISCT (International Society for Cell & Gene Therapy) definitions for clinical MSCs. [8] [9]

? CD31⁺

  • This is a marker of Endothelial Progenitor Cells (EPCs). [10]
  • It indicates vascular lineage and supports angiogenesis. [11]
  • It is found in regenerative matrices that promote blood vessel growth. [12]

? CD45–

  • The absence of this marker rules out hematopoietic (blood) lineage. [13]
  • It helps differentiate MSCs and EPCs from immune or leukocyte populations. [14]
  • It is critical for regulatory compliance and ensuring product purity. [15]

⚠️ Why are Cell Markers Controversial?

Some clinics claim “stem cells” but lack marker verification, meaning the product may be acellular or non-therapeutic. [16] The FDA and scientific authorities require marker-based characterization to validate the identity and purity of live-cell products. [17] Without this, products may fail to deliver the expected biological effects—or worse, contain undesired cell types. [16]

? What are the Dangers of Misidentified Markers?

Contaminants, such as CD45⁺ immune cells, may trigger unwanted immune reactions. [18] Missing key markers, such as CD73/CD90, means missing critical regenerative activity. [19] The use of unverified cell products can lead to inconsistent outcomes or safety issues. [20]

⚖️ Are Cell Markers Better Than PRP?

Cell markers are not a therapy but a tool for validation. [5] PRP lacks live cells and these markers, relying on platelet factors alone. [21] Marker-verified live cells in products like Cellular Wharton’s Jelly offer superior immunomodulation and repair potential. [22]

❌ Why are Cell Markers Not FDA Approved?

Markers are diagnostic tools, not therapies, but products using them must meet FDA criteria for HCT/Ps or biologics. [17] Cellular Wharton’s Jelly with these markers is regulated under IND protocols. [23]

⏳ How Long Do Marked Cells Last in the Body?

CD73⁺/CD90⁺ MSCs and CD31⁺ EPCs typically persist for days to weeks post-injection. [24] Their paracrine effects can endure months. [25]

? What in the Body Makes These Marked Cells?

MSCs (CD73⁺/CD90⁺) are produced in bone marrow, adipose, and umbilical tissues. [26] EPCs (CD31⁺) originate from bone marrow endothelium. [27] CD45– indicates non-hematopoietic origin. [28]

? Where Do These Marked Cells Come From (for Medical Use)?

They are sourced from umbilical cord (Wharton’s Jelly), bone marrow, or adipose tissue. [29] Cellular Wharton’s Jelly is rich in CD73⁺/CD90⁺ MSCs and CD31⁺ EPCs with CD45– profile. [30]

? What is the Best Source for These Marked Cells?

Cellular Wharton’s Jelly is optimal, providing a high yield of CD73⁺/CD90⁺ MSCs and CD31⁺ EPCs in a CD45– population. [31] It is immune-privileged and minimally processed. [32] [33]

? How Do You Get These Marked Cells?

Cells are isolated via enzymatic digestion and verified by flow cytometry. [34] Markers like CD73/CD90/CD31/CD45 are assessed using panels such as DURAClone. [35]

⚙️ How Do These Marked Cells Work?

CD73⁺/CD90⁺ MSCs modulate inflammation via adenosine production. [36] CD31⁺ EPCs drive angiogenesis. [37] CD45– ensures non-immunogenic profile. [38]

? Examples of Marked Cells in Regenerative Products

  • ? Cellular Wharton’s Jelly (CWJ): Contains CD73⁺/CD90⁺ MSCs and CD31⁺ EPCs for joint repair.
  • ? Bone Marrow Aspirate: Rich in CD45– HSCs and MSCs for bone regeneration.
  • ? Adipose SVF: Includes CD31⁺ EPCs for wound healing.

? Important Considerations for These Marked Cells

  • ✅ Marker verification ensures purity and efficacy. [8]
  • ❄️ Cryopreservation maintains marker expression. [24]
  • ? Heterogeneity varies by source. [26]
  • ⚠️ Unverified products risk contamination. [16]

? Summary

Therapeutic cell markers like CD73, CD90, CD31, and CD45 define cell identity and function in regenerative therapies, ensuring safety and efficacy.

In summary, cell markers serve as essential identifiers in regenerative medicine, guiding cell classification and therapeutic potential. From perinatal sources, they enable precise immunomodulation and repair in preclinical models. Standardization addresses controversies in characterization. Future advancements may refine marker-based therapies for optimized outcomes.

References

  1. Advances in regenerative therapy: A review of the literature and the application of adipose-derived stem cells for musculoskeletal disorders. Advances in regenerative therapy: A review of the literature and … https://pmc.ncbi.nlm.nih.gov/articles/PMC7033303/ [Peer-reviewed literature.]
  2. Adult Stem Cells: Beyond Regenerative Tool, More as a Bio-Marker in Modern Medicine. Adult Stem Cells: Beyond Regenerative Tool, More as a Bio-Marker … https://e-dmj.org/journal/view.php?doi=10.4093/dmj.2019.0175 [Peer-reviewed literature.]
  3. Fetal cardiac mesenchymal stem cells express embryonal markers and exhibit differentiation into multiple cell lineages. Fetal cardiac mesenchymal stem cells express embryonal markers … https://pmc.ncbi.nlm.nih.gov/articles/PMC3557348/ [Peer-reviewed literature.]
  4. Cell-free regenerative medicine: identifying the best source of regenerative factors in human umbilical cord blood. Cell-free regenerative medicine: identifying the best source of … https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1518412/full [Peer-reviewed literature.]
  5. Full spectrum flow cytometry reveals mesenchymal heterogeneity in first trimester placentae and phenotypic convergence in culture, providing insight into the origins of placental mesenchymal stromal cells. Full spectrum flow cytometry reveals mesenchymal heterogeneity in … https://elifesciences.org/articles/76622 [Peer-reviewed literature.]
  6. Markers and Methods to Verify Mesenchymal Stem Cell Identity, Potency, and Quality. Markers and Methods to Verify Mesenchymal Stem Cell Identity … https://resources.rndsystems.com/images/site/wp-msc-13763.pdf [Published non-peer-reviewed.]
  7. Comparison of the yields and properties of dedifferentiated fat cells and mesenchymal stem cells derived from infrapatellar fat pad in patients with knee osteoarthritis. Comparison of the yields and properties of dedifferentiated fat … https://www.sciencedirect.com/science/article/pii/S2352320422001134 [Peer-reviewed literature.]
  8. CD73+ Mesenchymal Stem Cells Ameliorate Myocardial Infarction by Promoting Angiogenesis. CD73+ Mesenchymal Stem Cells Ameliorate Myocardial Infarction … https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.637239/full [Peer-reviewed literature.]
  9. Markers and Methods to Verify Mesenchymal Stem Cell Identity, Potency, and Quality. Markers and Methods to Verify Mesenchymal Stem Cell Identity … https://resources.rndsystems.com/images/site/wp-msc-13763.pdf [Published non-peer-reviewed.]
  10. Mesenchymal Stem Cells Markers. Mesenchymal Stem Cells Markers https://juniperpublishers.com/oajnn/pdf/OAJNN.MS.ID.555561.pdf [Published non-peer-reviewed.]
  11. Anterior cruciate ligament-derived mesenchymal stromal cells have a propensity to differentiate into the ligament lineage. Anterior cruciate ligament-derived mesenchymal stromal cells have … https://www.sciencedirect.com/science/article/pii/S2352320417300470 [Peer-reviewed literature.]
  12. Phenotypical Characterization and Neurogenic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells. Phenotypical Characterization and Neurogenic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells https://www.mdpi.com/2073-4425/12/3/431 [Peer-reviewed literature.]
  13. MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. MSC surface markers (CD44, CD73, and CD90) can identify human … https://biosignaling.biomedcentral.com/articles/10.1186/s12964-015-0124-8 [Peer-reviewed literature.]
  14. Efficient Enrichment of Muse Cells from Human Umbilical Cord-Derived Mesenchymal Stromal Cells. Efficient Enrichment of Muse Cells from Human Umbilical Cord … https://bmrat.org/index.php/BMRAT/article/view/968 [Peer-reviewed literature.]
  15. Mesenchymal stem cells in lung diseases and their potential use in regenerative medicine. Mesenchymal stem cells in lung diseases and their potential use … https://www.elsevier.es/en-revista-clinics-22-articulo-mesenchymal-stem-cells-in-lung-S180759322300073X?covid=Dr56DrLjUdaMjzAgze452SzSInMN&rfr=truhgiz&y=kEzTXsahn8atJufRpNPuIGh67s1 [Peer-reviewed literature.]
  16. Immunophenotypic analysis of human adipose-derived stem cells and adipose-derived stem cell-derived endothelial cells. Immunophenotypic analysis of human adipose-derived stem cells … https://sci.amegroups.org/article/view/114519/html [Peer-reviewed literature.]
  17. Characterisation of mesenchymal stromal cells in clinical trial reports. Characterisation of mesenchymal stromal cells in clinical trial … https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02435-1 [Peer-reviewed literature.]
  18. Adipose stromal/stem cells in regenerative medicine: Potentials and limitations. Adipose stromal/stem cells in regenerative medicine: Potentials … https://www.wjgnet.com/1948-0210/full/v12/i1/1.htm [Peer-reviewed literature.]
  19. Evidence for CD34 as a Common Marker for Diverse Progenitors. Evidence for CD34 as a Common Marker for Diverse Progenitors https://academic.oup.com/stmcls/article/32/6/1380/6444497 [Peer-reviewed literature.]
  20. Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the addition of an enzymatic reagent. Isolation of adipose tissue derived regenerative cells from … https://www.biorxiv.org/content/10.1101/485318v3.full.pdf [Published non-peer-reviewed.]