Dermal Papilla Cells: The Cells That Decide Your Hair's Future

By Dr. Susan Lin, MD | MD HAIR | La Cañada Ventures, Inc.
Published on mdhair.com — Verbascoside & Lilac Science Series

You have been looking at the wrong part of your hair.

Not carelessly — everyone does it. You look at the hair you can see: the strand between your fingers, the shed hairs in the drain, the part in the mirror that photographs wider than it did two years ago. That is the only part available to you, so of course that is where your attention goes.

But the hair you can see is a dead protein filament. It has no cells, no metabolism, no ability to respond to anything. Whatever happened to it was decided months ago, several millimetres below your scalp, by a cluster of a few thousand cells you will never see.

That cluster is the dermal papilla. It is the reason one follicle produces a thick, pigmented, waist-length hair for six years and the follicle beside it produces a fine, short, colourless one for eight months. It is where androgens exert their effect. It is where the hair cycle is timed. And — this matters for anything you read on this site — it is the specific cell type where the published verbascoside research was actually conducted.

I am Dr. Susan F. Lin, M.D. I trained at Boston University School of Medicine, practised Obstetrics & Gynecology, and have formulated the MD® line at La Cañada Ventures, Inc. since 2008. This article is the keystone of our science cluster because almost every other article here eventually routes back to these cells. Once you understand what the dermal papilla does, most hair-loss marketing becomes legible — you can tell in about a sentence whether a claim is addressed to the follicle's decision-making apparatus or to the dead fibre it produced.

What the Dermal Papilla Actually Is

At the base of every hair follicle sits a bulb. Inside the bulb, wrapped in a cup of rapidly dividing epithelial cells called the hair matrix, sits a teardrop-shaped island of specialised connective-tissue cells: the dermal papilla.

Three facts about it are worth holding onto.

It is mesenchymal, not epithelial. The hair fibre itself is built by epithelial cells — matrix keratinocytes that divide, migrate upward, fill with keratin and die, becoming the hair shaft. The dermal papilla is a different lineage entirely. It descends from the dermis, it carries the follicle's blood supply into the bulb, and it does not become any part of the hair. It instructs.

It is small, and its size is not incidental. A terminal scalp follicle's papilla contains on the order of a few thousand cells. The number of papilla cells correlates with the volume of the hair the follicle produces — a larger papilla instructs a larger matrix, which builds a thicker fibre. This is not a metaphor; it is one of the more durable morphometric observations in hair biology, and it is the reason miniaturisation is fundamentally a story about papilla cell number and behaviour (Whiting, 2001; Stenn & Paus, 2001).

It carries instructive information, not just support. This is the finding that founded modern hair biology. In 1984, Jahoda, Horne and Oliver took dermal papilla cells from rat vibrissa follicles, cultured them, implanted them into ear skin that would never normally grow such a hair, and got hair follicles to form (Jahoda et al., 1984, Nature). The papilla did not merely feed a follicle. It told the overlying epithelium to become one.

Nearly thirty years later, Higgins and colleagues showed that human dermal papilla cells, which notoriously lose this inductive capacity in conventional flat culture, largely regain it when grown as three-dimensional spheroids — and could then induce de novo hair-follicle growth in human skin grafted onto mice (Higgins et al., 2013, PNAS). The instruction is real, it is intrinsic to these cells, and it is fragile enough to be lost when you culture them wrongly. Both halves of that sentence matter.

The signalling job, in plain terms

Molecular profiling of the papilla's signature — the genes it expresses that its neighbouring fibroblasts do not — has identified a distinctive set of signalling molecules and transcription factors that define what a papilla is (Rendl et al., 2005, PLoS Biology). Functionally, and without drowning you in pathway names, it does four things:

1. It sets the duration of growth. How many years a follicle stays in its growth phase is a papilla-governed property, not a property of the shaft.
2. It sets the calibre of the fibre. Papilla volume scales with hair diameter.
3. It relays systemic signals. Hormones, nutrients and inflammatory mediators arriving through the circulation are read here and translated into local instructions.
4. It regenerates the follicle at the end of each cycle. The lower follicle is dismantled and rebuilt every cycle; the papilla persists through that demolition and is the template for the rebuild.

That fourth point is the one people find most surprising, and it leads directly to the section that most readers of this site have come for.

Why Androgens Act Here, and Not on the Hair

If you have read our article on drug-free DHT blockers, you know the pathway: testosterone is converted by the enzyme 5-alpha-reductase into dihydrotestosterone, a more potent androgen, directly in peripheral tissues including scalp skin and hair follicles.

The enzyme exists in two isoforms, Type I and Type II, with different tissue distributions. Sawaya and Price measured both isoenzymes — along with aromatase and androgen receptor — directly in scalp follicles from women and men with androgenetic alopecia, establishing that both are present and measurable in the human scalp follicle system, with meaningful differences between the sexes (Sawaya & Price, 1997). Immunohistochemistry has since localised Type 2 within hair follicle structures and Type 1 predominantly in sebaceous glands (Bayne et al., 1999). Finasteride is a predominantly Type II-selective inhibitor; dutasteride inhibits both. That is mainstream, well-supported pharmacology and it stays.

But notice what all of that describes: where DHT gets made. It tells you the pressure. It does not tell you where the pressure lands.

Here is the answer, and it is the organising fact of this article. The androgen receptor that matters in hair biology is expressed in the dermal papilla. The matrix keratinocytes that physically build your hair shaft are not the primary androgen-responsive cells. The papilla is. Androgen binds its receptor in the papilla cell, and the papilla cell then changes what it says to the epithelium above it.

This is why androgen-driven hair loss is described in the literature as a paracrine process: the hormone acts on one cell type, which then alters the diffusible signals it sends to a different cell type, which is the one whose behaviour visibly changes (Inui & Itami, 2011). The dermal papilla is the interpreter. Everything downstream is translation.

What the papilla says when androgen is present

Two lines of evidence make this concrete.

Growth-inhibitory signalling. Balding-scalp papilla cells exposed to androgen produce more of certain inhibitory mediators. Kwack and colleagues showed that dihydrotestosterone induces DKK-1 in balding dermal papilla cells, and that DKK-1 in turn causes apoptosis in follicular keratinocytes — the cells building the hair (Kwack et al., 2008, Journal of Investigative Dermatology). The papilla receives the hormonal signal; the keratinocytes take the damage. Separately, TGF-β2 has been characterised as a papilla-derived mediator implicated in driving the human follicle out of growth phase (Hibino & Nishiyama, 2004).

Direct androgen toxicity to the papilla itself. Beyond changing what it says, sustained androgen exposure is also associated with loss of the papilla cells. That is the mechanism that makes miniaturisation progressive rather than merely a change in instruction — you are not only getting a worse instruction, you are getting it from a smaller and smaller committee.

And running alongside both is the second insult the dermatology literature now consistently describes: perifollicular micro-inflammation. Inflammatory infiltrates and perifollicular fibrosis are documented histological findings in male pattern alopecia (Jaworsky et al., 1992; Mahé et al., 2000; Deloche et al., 2004). Androgen signalling and inflammatory signalling converge on the same small cluster of cells.

Two insults, one target. Hold that phrase. It is why the evidence in the next section is relevant at all.

Lost Versus Dormant: The Distinction That Governs Everything

Patients ask me one question more than any other, in one form or another: is it gone, or is it asleep?

It is the right question and it has a real answer, though not a comfortable one. In 2011, Garza and colleagues examined bald scalp from men with androgenetic alopecia and found something important: the bald scalp retained its hair follicle stem cells. What it lacked was the population of CD200-rich, CD34-positive follicular progenitor cells — the downstream, more committed cells that stem cells give rise to in order to actually build a follicle (Garza et al., 2011, Journal of Clinical Investigation).

It cuts both ways. The hopeful reading: the reservoir is still there. Bald scalp in pattern hair loss is not empty scalp — the follicles are miniaturised, not absent, and the population that could in principle repopulate them persists. That is the biological basis for the clinical observation that pattern thinning responds to intervention in a way scarred, destroyed follicles never do. The sobering reading: a retained reservoir with a failed activation step is still a follicle producing a vellus hair. Presence is not function.

So the honest formulation is this:

Perifollicular fibrosis is the hinge between the second and third rows. It has been characterised as playing a pathogenetic role in androgenetic alopecia, not merely accompanying it (Yoo et al., 2006). When connective-tissue remodelling around a follicle progresses far enough, the architecture that a regenerating follicle needs is no longer there. That is the point at which asleep quietly becomes gone, and there is no bright line announcing when you crossed it.

Which is the entire clinical argument for acting early, and I make no apology for repeating it: the follicles you still have are the asset. Every intervention in this category, mine included, is better understood as protecting what is present than as resurrecting what is not.

Where the Verbascoside Evidence Actually Lives

Now the section this article was built to support.

MD Nutri Hair™ contains a lilac (Syringa vulgaris) extract standardised for verbascoside, a phenylethanoid glycoside. The reason I work with this molecule is not that it is a plant compound, and not that it is an antioxidant — hundreds of plant compounds are antioxidants and that is a weak reason to build a formulation. The reason is that the published research on it was run on human dermal papilla cells: exactly the cell type this entire article has been describing.

In 2022, Wisuitiprot and colleagues published a controlled laboratory study in Scientific Reports examining an Acanthus ebracteatus extract and verbascoside on human dermal papilla cells and on murine macrophages (Wisuitiprot et al., 2022; PMID 35087085; open access). Their framing is the same two-insult model I described above — androgen signalling plus micro-inflammation — which is why one study speaks to both halves.

In their laboratory experiments, verbascoside:

• Induced dermal papilla cell proliferation. Cell-cycle analysis showed treated cells shifting out of resting G1 and into G2/M — the signature of cells moving into active division. In the interest of precision: the S-phase fraction did not change meaningfully. I would rather give you the correct detail than the tidier one.
• Prevented testosterone-induced apoptosis of human dermal papilla cells. When the researchers exposed papilla cells to testosterone, the cells underwent programmed cell death. Verbascoside prevented it in that cell model, at statistical significance. This is the central finding of the paper and the central finding of this article.
• Reduced the release of pro-inflammatory signals — IL-1α and IL-6 from stressed dermal papilla cells, and IL-1β, TNF-α and nitric oxide from macrophages.

Now the constraints, stated as loudly as the findings, because they are not footnotes.

These were cell studies. In laboratory studies means in cells, in a dish. Cells in culture have no blood supply, no immune system, no hormonal axis and no hair cycle. The authors say so themselves: further clinical study is necessary to evaluate effectiveness. I will not claim more than the people who ran the experiment.

The verbascoside in that study did not come from lilac. The researchers used verbascoside sourced from Acanthus ebracteatus, a plant of traditional Thai medicine. It is the same defined molecule whichever plant it is drawn from — but the study was not run on MD's lilac-derived material and I will not imply that it was.

And a claim we removed. An earlier generation of our copy said verbascoside had been studied for interaction with 5-alpha-reductase. We held a supplier document saying so. When we pulled the primary source it cited, that paper turned out never to mention verbascoside at all — it tested two smaller molecules that are structural fragments of it, and its actual result pointed toward selectivity for one isoform rather than activity against both. The claim was not supported, so it is gone from every page we control. A citation is not evidence until someone opens it.

What remains is narrower and, I would argue, stronger: on the exact cell type where androgen-driven hair loss is decided, in laboratory conditions, this molecule kept those cells alive under a testosterone challenge and quietened the inflammatory signals around them.

The Bottom Line

The dermal papilla is a small cluster of mesenchymal cells at the base of each hair follicle, and it is the follicle's decision-making apparatus: it sets how long the growth phase lasts, how thick the fibre will be, and it rebuilds the lower follicle at the start of every cycle. Transplantation work established that these cells carry genuine inductive instruction rather than merely supporting the follicle (Jahoda et al., 1984; Higgins et al., 2013). Androgens matter in hair loss because the papilla is where the androgen receptor is expressed — DHT changes what the papilla says to the hair-building cells above it, through paracrine mediators including DKK-1 and TGF-β2 (Kwack et al., 2008; Hibino & Nishiyama, 2004; Inui & Itami, 2011) — and because sustained androgen and inflammatory pressure erodes the papilla itself. Bald scalp in pattern hair loss retains its stem cells but loses its progenitor population (Garza et al., 2011), which is why dormant and lost are genuinely different states, and why perifollicular fibrosis is the point where the difference stops being recoverable (Yoo et al., 2006). This is the cell type where the published verbascoside research was performed: in laboratory studies it induced dermal papilla proliferation, prevented testosterone-induced apoptosis, and reduced pro-inflammatory signals (Wisuitiprot et al., 2022). Those are cell studies, on verbascoside from a different botanical source, and their own authors call for clinical work. That is the whole claim, and it is deliberately no larger than that.

Dr. Susan Lin's Clinical Perspective

"When a patient sits down and tells me her hair is thinning, she is describing a fibre and I am thinking about a cluster of cells she cannot see and I cannot examine without a biopsy. That gap is where most of the confusion in this field lives. It is also why I hold formulation claims to a specific test: is the evidence on the cell that makes the decision, or on something downstream of it? A shampoo that improves shine has acted on dead keratin — useful, but it has not spoken to the papilla. When I evaluated verbascoside, what persuaded me was not that it was botanical or antioxidant. It was that the published work was performed on human dermal papilla cells under a testosterone challenge. The right cell, the right insult. It is still a dish, not a scalp, and I say so every time."

— Dr. Susan F. Lin, M.D., Physician Formulator, MD HAIR

Mechanism Spotlight: Why the Papilla Survives Its Own Follicle's Demolition

The strangest thing about the hair follicle is that it destroys and rebuilds most of itself several times in your life, on purpose.

At the end of the growth phase, the lower two-thirds of the follicle — the bulb, the matrix, the pigment-producing melanocytes — regresses through a controlled process of apoptosis, drawing the follicle upward toward the skin surface (Stenn & Paus, 2001; Paus & Cotsarelis, 1999). Almost the entire growth apparatus is dismantled.

The dermal papilla is not. It condenses, travels upward with the regressing follicle, and comes to rest beneath the bulge region — the stem-cell reservoir in the upper follicle. There it waits. When the next cycle begins, the papilla and the bulge stem cells re-establish contact, and the reconstituted signalling between them rebuilds the entire lower follicle from scratch.

This is why the papilla is the organ of continuity. It is the memory that carries a follicle's identity across the gap between one hair and the next.

And it is why anything that reduces papilla cell number is so consequential. A hair shaft lost to breakage is replaced. A cycle lost to a stressor resumes. But papilla cells lost to sustained androgen and inflammatory pressure are lost from the template that will build every subsequent hair — and the follicle rebuilds itself smaller (Whiting, 2001; Garza et al., 2011). The regeneration is faithful. That is exactly the problem: it faithfully reproduces a diminished instruction.

Recommended Reading

Pillar pages on mdhair.com:

• The Lilac & Verbascoside Science — the pillar this article anchors
• Drug-Free Hair Loss Treatment — The Complete Guide
• Hormonal Hair Loss
• The Clinical Evidence Behind MD HAIR

Related articles in this series:

• What Is Verbascoside? The Plant Compound Behind MD Nutri Hair — the molecule itself, and where its evidence begins and ends
• Beyond Saw Palmetto: The Drug-Free DHT Blockers That Have Evidence — the androgen pathway that arrives at these cells, and how to read botanical claims about it
• PCOS and Hair Loss — the clearest clinical picture of androgen pressure on the papilla in women

Our sister site md-factor.com carries the wider MD® line and the customer reviews for MD Nutri Hair™, for readers who want to see how people describe their own experience over months rather than weeks.

MD HAIR Product Recommendation

MD Nutri Hair™ — /products/nutri-hair-supplement

Why this product, for this article specifically. The dermal papilla sits several millimetres below the skin surface, wrapped in the follicle's own blood supply — which is the reason an internal arm exists in this protocol at all. MD Nutri Hair™ is the formulation in our line that carries the standardised lilac verbascoside discussed above, the molecule whose published research was performed on this exact cell type.

The mechanism sentence, stated precisely. In laboratory studies on human dermal papilla cells, verbascoside reduced the release of pro-inflammatory signals including IL-1α, IL-6, IL-1β and TNF-α, and prevented testosterone-induced death of those cells. Those are cell studies, not clinical trials, and that is exactly how I want you to hold them. We do not claim that verbascoside inhibits 5-alpha-reductase, because the evidence for that claim did not survive being read.

What is in it, from the label. One capsule daily, for adults. A Proprietary Blend of 300 mg, plus niacinamide 5 mg, vitamin E as alpha tocopheryl acetate 5 mg, and D-biotin 0.05 mg. Other ingredients: flaxseed powder, lignan powder, lilac. Proprietary blend means the individual amounts of flaxseed, lignan and lilac are not disclosed — that is lawful, it is common, and it is our weakest transparency answer. I would rather tell you than have you work it out.

One thing I will defend: biotin at 0.05 mg is a cofactor dose, roughly a hundredfold below the levels at which biotin is generally cited as interfering with immunoassay laboratory tests. If you are having thyroid or cardiac blood work, a megadose biotin supplement can distort it. This one is not that.

Per the product label: do not take if you are pregnant or breast feeding.

A note on authenticity: genuine MD HAIR™ and MD Nutri Hair™ products are sold only through mdhair.com, md-factor.com, and the official La Cañada Ventures, Inc. stores on Amazon and Walmart.

Not sure whether androgen pressure is what is driving your thinning? Take the MD HAIR Quiz — several of its outcomes route you to a physician and a laboratory panel rather than to any product of ours.

References

1. Wisuitiprot V, Ingkaninan K, Chakkavittumrong P, Wisuitiprot W, Neungchamnong N, Chantakul R, Waranuch N. (2022). Effects of Acanthus ebracteatus Vahl. extract and verbascoside on human dermal papilla and murine macrophage. Scientific Reports, 12(1), 1491. PMID 35087085 · open access
2. Jahoda CA, Horne KA, Oliver RF. (1984). Induction of hair growth by implantation of cultured dermal papilla cells. Nature, 311(5986), 560–562. PMID 6482967
3. Higgins CA, Chen JC, Cerise JE, Jahoda CA, Christiano AM. (2013). Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. PNAS, 110(49), 19679–19688. PMID 24145441
4. Rendl M, Lewis L, Fuchs E. (2005). Molecular dissection of mesenchymal-epithelial interactions in the hair follicle. PLoS Biology, 3(11), e331. PMID 16162033
5. Yang CC, Cotsarelis G. (2010). Review of hair follicle dermal cells. Journal of Dermatological Science, 57(1), 2–11. PMID 20022473
6. Stenn KS, Paus R. (2001). Controls of hair follicle cycling. Physiological Reviews, 81(1), 449–494. PMID 11152763
7. Paus R, Cotsarelis G. (1999). The biology of hair follicles. New England Journal of Medicine, 341(7), 491–497. PMID 10441606
8. Inui S, Itami S. (2011). Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla. Journal of Dermatological Science, 61(1), 1–6. PMID 21167691
9. Kwack MH, Sung YK, Chung EJ, et al. (2008). Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. Journal of Investigative Dermatology, 128(2), 262–269. PMID 17657240
10. Hibino T, Nishiyama T. (2004). Role of TGF-beta2 in the human hair cycle. Journal of Dermatological Science, 35(1), 9–18. PMID 15194142
11. Garza LA, Yang CC, Zhao T, et al. (2011). Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. Journal of Clinical Investigation, 121(2), 613–622. PMID 21206086
12. Whiting DA. (2001). Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. Journal of the American Academy of Dermatology, 45(3 Suppl), S81–S86. PMID 11511857
13. Sawaya ME, Price VH. (1997). Different levels of 5α-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. Journal of Investigative Dermatology, 109(3), 296–300. PMID 9284093
14. Bayne EK, Flanagan J, Einstein M, et al. (1999). Immunohistochemical localization of types 1 and 2 5α-reductase in human scalp. British Journal of Dermatology, 141(3), 481–491. PMID 10583052
15. Randall VA. (2008). Androgens and hair growth. Dermatologic Therapy, 21(5), 314–328. PMID 18844710
16. Jaworsky C, Kligman AM, Murphy GF. (1992). Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis. British Journal of Dermatology, 127(3), 239–246. PMID 1390168
17. Mahé YF, Michelet JF, Billoni N, et al. (2000). Androgenetic alopecia and microinflammation. International Journal of Dermatology, 39(8), 576–584. PMID 10971723
18. Deloche C, de Lacharrière O, Misciali C, et al. (2004). Histological features of peripilar signs associated with androgenetic alopecia. Archives of Dermatological Research, 295(10), 422–428. PMID 14758487
19. Yoo HG, Kim JS, Lee SR, et al. (2006). Perifollicular fibrosis: pathogenetic role in androgenetic alopecia. Biological & Pharmaceutical Bulletin, 29(6), 1246–1250. PMID 16755026
20. Alipieva K, Korkina L, Orhan IE, Georgiev MI. (2014). Verbascoside — a review of its occurrence, (bio)synthesis and pharmacological significance. Biotechnology Advances, 32(6), 1065–1076. PMID 25048704
21. MD Nutri Hair™ box artwork, June 2016 — Supplement Facts panel, Other Ingredients and label warnings, as quoted. Internal document, on file.
22. Phytostem VitaFoods Lilac Dry 50N raw-material specification, product code DC2581N, Resources of Nature LLC, revision 07/13/2011 — Syringa vulgaris leaf cell culture extract; verbascoside 47.5–52.5% w/w by HPLC. Internal document, on file.

Dr. Susan F. Lin, M.D. is the physician formulator behind MD HAIR and MD Nutri Hair™, product lines of La Cañada Ventures, Inc. — physician-formulated since 2008 under the MD® mark (U.S. Reg. No. 4,471,494). She trained at Boston University School of Medicine and is board-certified in Obstetrics & Gynecology and in Anti-Aging Medicine (A4M).

This article is for educational purposes and does not constitute medical advice. Consult your own physician for personalized guidance, particularly if your hair loss is sudden, patchy, painful, or accompanied by scalp scarring.

MD® products are cosmetics and dietary supplements manufactured in FDA-registered, GMP-compliant facilities. "FDA-registered" describes the facility, never the product: no MD product is FDA approved, and no cosmetic or dietary supplement is. Individual results vary. MD Nutri Hair™ is a dietary supplement. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

MD Nutri Hair™ is for adults only, one capsule daily. Per the product label: do not take if you are pregnant or breast feeding. Because there are no clinical data in pregnant or breastfeeding women, we do not advocate using MD HAIR products during pregnancy or lactation.

Laboratory findings described in this article were obtained in cell culture. They are not clinical outcomes and are not presented as such.

Explore more in the Verbascoside & Lilac Science series at mdhair.com/pages/lilac-verbascoside-science