1. Medicinal plant stem cells and their applications
Plant stem cells are undifferentiated cells found in meristematic tissues that possess the ability to self-renew and differentiate into specialized cell types, making them essential for plant growth, development, and regeneration [
1,
2]. They are categorized into three main types: apical meristems, located at the tips of roots and shoots, which drive primary growth; lateral meristems, found in vascular and cork cambium, which contribute to secondary growth and thickening of stems and roots; and intercalary meristems, present in monocots, such as grasses, which enable regrowth after cutting. These stem cells have significant applications across various industries, including agriculture and plant breeding, where they enhance plant regeneration, propagation, and stress tolerance against adverse environmental conditions, such as drought, disease, and extreme temperatures [
3,
4]. In the cosmetics and skincare industries, plant stem cells, particularly those derived from apples (
Malus domestica), grapes (
Vitis vinifera), and edelweisses (
Leontopodium alpinum), are valued for their high antioxidant content and regenerative properties, making them popular ingredients in anti-aging and skin repair formulations [
5,
6]. In medicine and biotechnology, plant stem cells have the potential to produce plant-derived pharmaceuticals and bioengineered compounds, supporting sustainable drug synthesis without relying on large-scale farming [
7]. Additionally, they serve as sustainable alternatives in plant tissue culture, allowing the efficient production of bioactive compounds without extensive use of natural resources. Given their broad applications and potential to revolutionize multiple industries, plant stem cells continue to be a vital area of research and innovation.
Medicinal plant stem cells, derived from plants with therapeutic properties, offer immense potential in pharmaceuticals, biotechnology, and skincare. Derived from meristematic tissues, these cells can regenerate, proliferate, and differentiate into various specialized cells while retaining high concentrations of bioactive compounds, such as antioxidants, polyphenols, flavonoids, and alkaloids [
7,
8]. Unlike traditional plant extraction methods, stem cell technology enables sustainable and controlled production of valuable medicinal compounds without harming the plant population, making it an eco-friendly alternative to wild harvesting. Medicinal plant stem cells have numerous applications, including the development of plant-based drugs that are used to synthesize bioactive molecules with anti-inflammatory, antimicrobial, and anticancer properties. Notable examples include stem cells from
Tripterygium wilfordii [
9], which are known for their anti-inflammatory and immune-boosting effects, and
Catharanthus roseus [
10], which are valued for their anticancer properties. Medicinal plant stem cells also drive the development of skincare and cosmetic industries, where they contribute to anti-aging, skin rejuvenation, and repair formulations because of their ability to stimulate collagen synthesis, protect against oxidative stress, and promote cell regeneration [
6]. Furthermore, in regenerative medicine and biotechnology, medicinal plant stem cells are being explored for their role in tissue engineering [
11] and production of plant-based pharmaceuticals [
12], offering a promising avenue for future drug development. By utilizing plant stem cell cultures, researchers can enhance the production of rare and potent medicinal compounds, ensuring consistent quality, high purity, and a sustainable supply, ultimately revolutionizing the development of plant-derived medicines and cosmeceuticals (
Fig. 1).
2. Medicinal plant stem cells as a source of bioactive products
Medicinal plant stem cell-derived bioactive products have shown therapeutic potential for a range of conditions, including cardiovascular diseases, neurodegenerative disorders, and microbial infections. The pharmaceutical industry is increasingly exploring the use of medicinal plant stem cells for drug development. For instance,
Taxus baccata (European yew) stem cells are a sustainable source of paclitaxel, a critical anticancer compound [
13]. In addition to pharmaceuticals, medicinal plant stem cells have extensive applications in the cosmetic and skincare industries. Rich in antioxidants and regenerative compounds, they help protect the skin from oxidative stress, stimulate collagen production, and support skin renewal. For example,
Echinacea purpurea stem cell extracts, used in products such as “Echinacea Stems GX™”, are marketed in skincare for their potential to stimulate collagen synthesis, reduce capillary permeability, and reinforce the capillary wall, addressing signs of aging, while products like “First Botany, pure
Aloe vera gel” claim to be infused with collagen, stem cells, and other ingredients.
Advances in biotechnology have further enhanced the scalability and efficiency of plant stem cell cultures through bioreactor-based techniques, enabling the large-scale production of bioactive compounds under controlled conditions [
7,
14]. By harnessing plant stem cell technology, researchers and industries can achieve a sustainable, eco-friendly, and highly efficient approach for producing valuable bioactive compounds for health and wellness applications. The proposed Global Medicinal Plant Stem Cell Bank aims to preserve and facilitate the global sharing of diverse medicinal plant resources [
15]. With ongoing research, medicinal plant stem cells are emerging as promising alternatives to traditional plant extracts, paving the way for the next generation of plant-based pharmaceuticals and cosmeceuticals.
3. Future perspectives
Plant stem cell research faces several limitations, including an incomplete understanding of the underlying molecular mechanisms, difficulties in isolating and culturing them, and challenges in directing their differentiation. Efficient large-scale production remains hindered by genetic instability, scalability issues, and high costs associated with bioreactor systems. Regulatory and ethical concerns, particularly for genetically modified applications, also impact commercialization. Additionally, translating laboratory research into real-world agricultural and industrial applications is challenging due to environmental stressors and variable field conditions. Despite these challenges, advancements in genomics, spatial omics, clustered regularly interspaced short palindromic repeats (CRISPR) technology, and synthetic biology hold promise for overcoming these limitations and expanding the potential applications of plant stem cells in agriculture, medicine, and biotechnology. For example, the development of single-cell isolation technology using specific molecular probes or CRISPR/CRISPR-associated protein 9 (Cas9) gene markers could improve the efficiency and purity of plant stem cells.
3.1. Understanding gene regulation
Plant stem cell regulation is a complex process governed by interconnected transcriptional networks, transcription factors (TFs), signal transduction pathways, and kinase-mediated modifications, that ensure stem cell maintenance, differentiation, and adaptation to environmental conditions. At the core of this regulatory system are transcriptional networks that integrate multiple signals to control the balance between stem cell renewal and specialization. In the shoot apical meristem (SAM), the WUSCHEL (
WUS)-mediated network interacts with CLAVATA (
CLV) genes to maintain stem cell homeostasis through a feedback loop. In the root apical meristem (RAM), PLETHORA (
PLT) TFs establish positional cues that define stem cell niches [[
16], [
17], [
18], [
19], [
20]]. These networks coordinate hormonal signals and external stimuli to fine-tune plant growth and development. TFs play crucial roles in regulatory networks in plant stem cells by acting as activators or repressors of target genes. Members of the WUSCHEL-related homeobox (
WOX) family, such as
WUS in SAM and
WOX5 in RAM, promote stem cell identity and quiescent center maintenance, respectively [
19,
21]. The APETALA2/ethylene response factor family, including
PLT1 and
PLT2, directs the root stem cell fate [
22], whereas SHORT-ROOT (
SHR) and SCARECROW (
SCR) from the GRAS family regulate asymmetric cell division and radial patterning [
23]. Additionally, SPEECHLESS (
SPCH) and MUTE from the basic helix–loop–helix (
bHLH) family are essential for stomatal lineage specification, highlighting the diverse roles of TFs in stem cell differentiation and organ formation [
24]. These TFs function in cascades to form regulatory loops that either maintain stem cell identity or initiate differentiation when required. Key questions remain regarding how these TFs exhibit distinct functions across different cell types while also playing broader roles in organ development.
Signal transduction pathways further modulate stem cell behavior by relaying extracellular signals to transcriptional regulators, thereby ensuring a precise developmental response. The
CLV–WUS pathway in SAM involves CLV3, a secreted peptide ligand that binds to CLV1 receptor-like kinase, initiating a cascade that represses
WUS expression, thereby controlling stem cell proliferation [
25]. In RAM, auxin signaling mediated by PIN-FORMED (
PIN) transporters establishes an auxin gradient that regulates
PLT transcription and guides root meristem development [
26]. Hormonal crosstalk between auxin and jasmonate signaling also plays a crucial role in the regulation of regeneration [
27]. Cytokinin signaling is another critical pathway that promotes stem cell proliferation in SAM by activating
WUS expression [
28]. Other hormones, such as brassinosteroids, abscisic acid, and gibberellins, further influence meristem maintenance and differentiation by interacting with core regulatory mechanisms [
29]. Despite significant progress, several aspects of hormonal regulation of plant stem cells remain unclear. The precise molecular mechanisms underlying the crosstalk between hormones and their spatiotemporal distribution in stem cell niches have not been fully elucidated. How hormones interact with epigenetic modifications to control stem cell fate, the detailed mechanisms of hormone transport beyond auxin, and the role of non-traditional signals such as peptides and reactive oxygen species (ROS) in hormonal regulation require further exploration [[
30], [
31], [
32]].
Kinases play a pivotal role in stem cell regulation by phosphorylating key proteins that modulate their activity, stability, and interactions. Receptor-like kinases such as CLV1, CLV2, and CORYNE (CRN) are essential in the
CLV–WUS pathway, ensuring proper stem cell homeostasis [
33]. Mitogen-activated protein kinases (MAPKs) contribute to stress response signaling and meristem activity by modifying TF functions [
34]. Despite advances in the understanding of kinases in plant stem cell regulation, several gaps remain, including the identification of unknown kinases and their specific roles, as well as their complex interactions with downstream targets. The crosstalk between different kinase-mediated signaling pathways, along with the regulatory mechanisms controlling kinase activation, inhibition, and post-translational modifications, is not fully understood. Additionally, the impact of environmental factors on kinase activity, spatiotemporal dynamics of kinase signaling within meristems, and evolutionary conservation of these mechanisms across plant species remain unclear. Functional redundancy among kinases further complicates the identification of their specific roles, making it challenging to determine how different kinases compensate for each other.
Collectively, transcriptional networks, TFs, signaling pathways, and kinases create a tightly regulated system that governs plant stem cell maintenance and differentiation. These regulatory mechanisms not only ensure proper plant development but also allow adaptation to environmental stresses, making them essential for plant growth and survival. A deeper understanding of these processes offers valuable insights for agricultural advancements, including crop improvement, stress resilience, and tissue regeneration through genetic and biotechnological approaches.
3.2. Genomics-driven stem cell research
Genomics-driven stem cell research leverages advanced sequencing technologies, transcriptomics, and bioinformatics to elucidate the genetic and molecular mechanisms governing stem cell function, differentiation, and regeneration. In plants, this approach helps identify key genes, regulatory networks, and epigenetic modifications that control stem cell maintenance within meristems, which allows precise manipulation of plant growth, development, and stress responses. High-throughput sequencing and single-cell RNA sequencing (scRNA-seq) provide insights into stem cell heterogeneity and lineage specification [[
35], [
36], [
37], [
38]]. Editing
cis-regulatory elements within the promoters of developmental regulators affects gene expression, leading to changes in meristem organization [
39]. Comparative genomics has facilitated the discovery of conserved and species-specific stem cell regulatory pathways. Despite its potential, challenges, such as data complexity and functional validation of genomic findings, must be addressed to fully harness genomics for plant stem cell research and applications.
In addition to sequencing, the integration of omics technologies, including genomics, transcriptomics, spatial transcriptomics, proteomics, metabolomics, and epigenomics, has provided a system-level understanding of biological processes. By combining these diverse data layers, researchers can investigate gene expression dynamics, protein interactions, metabolic pathways, and epigenetic modifications, thereby providing new insights into plant cell regeneration. Multi-omics approaches have facilitated the identification of metabolic pathway genes and optimized the biotechnological applications of medicinal plants [
40,
41]. The proposed “1 K Herb Genome Project” will provide multi-omics resources for elucidating biosynthetic pathways, facilitating synthetic biology approaches for producing bioactive compounds, and promoting further development of medicinal plant stem cells [
42]. Multi-omics research on plant stem cells faces several limitations, including challenges in achieving high-resolution, cell-type-specific data, owing to the small size and complexity of stem cell niches. Technical constraints, especially in proteomics and metabolomics, arise because of plant-specific factors, such as cell wall interference and secondary metabolites. Overcoming these challenges requires advances in single-cell and spatial omics, improved computational methods, and expanded plant-specific reference databases.
CRediT authorship contribution statement
Ranran Gao: Writing – original draft. Yuhua Shi: Writing – review & editing. Yuanzhu Liu: Data curation. Ling Yuan: Writing – original draft. Li Xiang: Writing – review & editing, Supervision.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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