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Mesoderm layer and fibrous support tissues essential for embryological differentiation
Medical Hypotheses (2002) 59(6), 630–635 ª 2002 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0306-9877(02)00160-3, available online at http://www.idealibrary.com
Mesoderm layer and fibrous support tissues essential for embryological differentiation Y. Hirata, S. Hirata Hirata Hospital, Kochi, Nippon, Japan
Summary Of the three germ layers, the mesoderm layer is the first to differentiate from the blastula and continues to lead the embryological differentiation while initiating the secretion of antagonistic duplication and maturation factors. After differentiation and while maintaining the secretion of duplication and maturation factors, the fibrous tissues that differentiated from mesoderm play an essential role in regulating the physio-mitotic conditions of functional tissues found in all histological organizations. Accordingly, some defects in mitotic interaction between the fibrous and functional tissues organized into structural units may give rise to various diseases such as carcinoma, sarcoma, leukemia, and fibro-multiplastic, myo-atrophic and neuroatrophic diseases. This defect in mitosis suggests the most important step in achieving eradication of these diseases. ª 2002 Elsevier Science Ltd. All rights reserved.
INTRODUCTION According to physio-mitotic theory described by Hirata (1–5), all organic tissues maintain their histological identity and continuity through a prescribed volume of functional cells. In the gastric mucous for example (Figs. 1 and 2), the stem cells continuously replicate through duplication mitosis within duplication areas (i.e., basal potion of the gland crypts), where they are subjected to the effect of duplication factor derived from the surrounding fibrous tissue. Most of the replicated stem cells are then pushed out of the duplication areas into the maturation zones (i.e., lateral portion of the gland crypts) by the volume of replicated cells. In the maturation zones that are subjected to the effect of maturation factor, the duplication mitosis of stem cells is converted to maturation mitosis by the maturation factor also derived
Received 25 June 2001 Accepted 13 February 2002 Correspondence to: Yoso Hirata MD, Hirata Hospital, 5-4-23 Hommachi, 780-0870 Kochi, Nippon, Japan. Phone: +81-888-75-6221; Fax: +81-888-713801; E-mail: [email protected]
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from the nearest fibrous tissue supporting the zones. Through a prescribed number of maturation mitotic phases, the displaced stem cells gradually mature, or differentiate, into a predetermined number of terminally matured functional end cells with a prescribed life span, and thus comprise the functional areas of the mucous layer. These functional end cells eventually die, and are then replaced by the subsequent generations of terminal end cells. This cell turnover is continuous and maintains constant volume of functional cells in the mucous layer. The duplication mitosis of the stem cells remaining in the duplication areas supplies cells to the maturation zones while also supplying cells to the duplication areas, thus establishing the histological identity and continuity of the gastric mucosa. Conversely, the maturation mitosis does not contribute to establishing the histological identity and continuity.
PHYSIO-MITOTIC DEVELOPMENTS AND FIBROUS TISSUES In the example of gastric mucosa, the factor regulating the duplication areas is specifically derived from fibrous
Mesoderm layer
631
Fig. 1 Gastric mucous layer (Glandula).
Fig. 2 Two types of mitosis in the gland crypt.
tissues in direct contact with the areas. The maturation zones and all sites outside of the duplication areas are constantly subjected to the effect of maturation factor, which is also derived from the nearest supporting fibrous tissues. Consequently, the two types of mitosis occurring in the gland crypts are maintained by the two different factors, which are secreted concomitantly from ª 2002 Elsevier Science Ltd. All rights reserved.
the supporting fibrous tissues themselves. Thus the gastric mucosa is maintained by the fibrous tissues, and is supported by capillary beds found within the fibrous tissues. In principle, all histological organizations include fibrous support tissues, and these fibrous tissues regulate and preserve normal mitotic conditions by producing the duplication and maturation factors. These Medical Hypotheses (2002) 59(6), 630–635
632 Hirata and Hirata
essential fibrous tissues differentiated during embryogenesis since the three germ layers are derived from the blastula. DIFFERENTIATION OF MESODERM LAYER During the first embryological mitotic duplications, a fertilized cell replicates and forms a spherical blastula (Fig. 3). When the blastula reaches a certain size, some of the cells migrate into the blastula sphere. These cells then differentiate into the mesodermal cells under the influence of the surrounding blastula cells. As these mesodermal cells continue to replicate through duplication mitosis, the first effect of maturation factor is exerted from the cells themselves, and functions to convert the duplication mitosis of blastula cells into the first matu-
ration (i.e., differentiation) mitosis within the blastula sphere. The resultant cells then invaginate into the blastula, and are thus surrounded by mesoderm forming the endodermal germ layer. The remaining blastula cells in contact with the external surface of the mesoderm layer then differentiate into the third germ layer, the ectoderm, without migrating into the blastula. Thus, formation of the three germ layers is accomplished (Fig. 3). Throughout the process, the mesoderm layer differentiated first, and initiated the formation of all three germ layers. The duplication mitosis within the mesoderm layer constitutively produces a maturation factor, which might convert duplication mitosis to maturation within the ectoderm and endoderm layers. Through the converted maturation mitosis, the duplication factor for the mesoderm layer is synergistically produced from the
Fig. 3 Diagram showing formation of the three germ layers.
Medical Hypotheses (2002) 59(6), 630–635
ª 2002 Elsevier Science Ltd. All rights reserved.
Mesoderm layer
ectoderm and endoderm layers. Conversely, the duplication mitosis within the ectoderm and endoderm layers produces the antagonistic maturation factor for the mesoderm layer. Consequently, the mesoderm layer and the ectoderm and endoderm have antagonistic and synergistic interactions. During these complex mitotic developments, each germ layer creates its own maturation conditions involving a large number of duplication areas. During the mitosis of the differentiating mesoderm layer, each of the duplication areas surrounded by the maturation zones is invaginated into the mesoderm layer to form a histological structural unit of differentiation (Fig. 4). Since the mesoderm surrounding the
633
structural units was the first germ layer to differentiate in the blastula, it alone initiates the formation of the structural units comprising the germ layers, while continually providing the duplication and maturation factors. Accordingly, the genesis and degeneration of the structural units is controlled by the mitotic conditions of the surrounding mesoderm layer. In summary, all developing functional tissues, including various hemocytoblasts differentiated from the mesoderm, require the fibrous support tissues that are also differentiated from mesoderm through mesenchyme. During differentiation from individual germ layers to functional tissues, a large number of the structural units
Fig. 4 Diagram showing the embryological differural unit of the intestinal mucosal tissue.
ª 2002 Elsevier Science Ltd. All rights reserved.
Medical Hypotheses (2002) 59(6), 630–635
634 Hirata and Hirata
Fig. 5 Diagram showing the segmentation of structural unit.
comprising individual germ layers must be gradually differentiated into functional tissues. These differentiated structural units are always surrounded by fibrous support tissues, which regulate them by concomitantly producing antagonistic duplication and maturation factors.
ESSENTIAL ROLE OF FIBROUS TISSUES As previously described by Hirata (6), in the example of intestinal mucosa, a prescribed volume of functional end cells is produced from a single duplication areas (i.e., basal portions of a gland crypt). This volume of cells forms the structural units of the entire functional
Fig. 6 Diagram showing the degeneration of a structural unit.
Medical Hypotheses (2002) 59(6), 630–635
ª 2002 Elsevier Science Ltd. All rights reserved.
Mesoderm layer
mucous tissue (Fig. 4). Consequently, an increase in the number of duplication areas that may result from an over-production of the duplication factor by the supporting fibrous tissues may cause a progressive increase in growth of the functional mucosa (Fig. 5). Conversely, degeneration of the duplication areas may result from replacement of the duplication factor by maturation factor produced by other fibrous tissues, and may gives rise to a progressive decrease in the growth of the functional mucosa (Fig. 6). This fluctuation in the number of duplication areas is dependent on the mitotic activity within these areas, reflected in the density of structural units comprising the functional tissues. These structural units (Fig. 4) are each surrounded by fibrous support tissues, derived from mesoderm that produces the different duplication and maturation factors. Although the mitosis occurring in these fibrous tissues might not be identifiable as duplication or maturation types, the fibrous tissues, may consist of two physio-mitotic layers: the maturation and duplicative layers. The maturation layers are juxtaposed on the duplication areas and provide the duplication factor. In contrast, the duplication layers support the maturation zones surrounding the areas and produce the maturation factor, which may initiate and regulate the progression from stem cell to functional end cell while also regulating the functional areas outside of the duplication areas. Throughout these mitotic progressions, a large number of histological structural units, with their fibrous support tissues, are maintained at a given volume within the tissues by the intrinsic ability of the supporting fibrous tissues, to exert concomitantly the two different effects of duplication and maturation factors. Since the three germ layers are derived from the blastula, through the fluctuations in the number of the structural units, every functional tissue would individually differentiate from one of the three germ layers. CONCLUSION The fibrous tissues that differentiate from mesoderm while enveloping the histological structural units within tissues are responsible for initiating the differentiation from the three germ layers to the functional tissues. Following differentiation, the fibrous support tissues continue to play an essential role in regulating the mitotic conditions of these structural units by concomitantly producing the antagonistic duplication and maturation factors. Consequently, to regulate the functional tissues, the fibrous support tissues have two
ª 2002 Elsevier Science Ltd. All rights reserved.
635
functional layers: the duplication layers which secrete the maturation factor in the maturation zones, and the maturation layers, which secrete the duplication factor for the stem cells within the duplication areas. Thus, all functional tissues maintain a constant volume of cells through maintaining the appropriate mitotic conditions. Consequently, the fibrous support tissues play an essential role in maintaining the physio-mitotic conditions of normally functioning tissues, in addition to supporting the histological organization that includes capillary beds investing the fibrous tissues themselves. However, in reality, certain diseases develop due to an imbalance in the mitotic conditions. As described by Hirata (1–4), cancer development may physio-mitotically be dependent on a certain cellular peculiarity interfering with the effect of maturation factor provided by fibrous tissues. Leukemia development may also be dependent on a general deterioration in the effect of maturation factor for leuko-blastcysts, without depending on a certain cellular defect in the maturability of individual leuko-blastcysts (5–7). However, various other diseases including fibro-multiplastic, myoatrophic, and neuroatrophic diseases may also develop due to some imbalance in mitotic interaction between the fibrous and functional tissues. Proper balance might be restored through the use of either duplication or maturation factors that would interact with the fibrous and functional cells. This approach may be the most important step in eradicating these diseases.
REFERENCES 1. Hirata Y. Duplication mitosis in epithelio-glandular tissue. Med Hypotheses 1992; 37: 44–46. 2. Hirata Y. Hetero-duplication type of cancerous mitosis. Med Hypotheses 1993; 41: 509–512. 3. Hirata Y. Established histological identity and cell destruction treatment for cancer. Med Hypotheses 2000; 55(1): 15–23. 4. Hirata Y. A physio-mitotic theory and new concept of cancer development. Med Hypotheses 2002; 58(5): 361–364. 5. Hirata Y. A physio-mitotic theory and new concept of leukemia development. Med Hypotheses 2002; 58(4): 251–253. 6. Hirata Y. A physio-mitotic theory and new concept of embryo-logical differentiation. Med Hypotheses 2002; 58(5): 365–368. 7. Hirata Y. Leukemia eradication and the effect of maturation factor. Med Hypotheses 2002; 58(5): 369–370.
Medical Hypotheses (2002) 59(6), 630–635
Mesoderm layer and fibrous support tissues essential for embryological differentiation Y. Hirata, S. Hirata Hirata Hospital, Kochi, Nippon, Japan
Summary Of the three germ layers, the mesoderm layer is the first to differentiate from the blastula and continues to lead the embryological differentiation while initiating the secretion of antagonistic duplication and maturation factors. After differentiation and while maintaining the secretion of duplication and maturation factors, the fibrous tissues that differentiated from mesoderm play an essential role in regulating the physio-mitotic conditions of functional tissues found in all histological organizations. Accordingly, some defects in mitotic interaction between the fibrous and functional tissues organized into structural units may give rise to various diseases such as carcinoma, sarcoma, leukemia, and fibro-multiplastic, myo-atrophic and neuroatrophic diseases. This defect in mitosis suggests the most important step in achieving eradication of these diseases. ª 2002 Elsevier Science Ltd. All rights reserved.
INTRODUCTION According to physio-mitotic theory described by Hirata (1–5), all organic tissues maintain their histological identity and continuity through a prescribed volume of functional cells. In the gastric mucous for example (Figs. 1 and 2), the stem cells continuously replicate through duplication mitosis within duplication areas (i.e., basal potion of the gland crypts), where they are subjected to the effect of duplication factor derived from the surrounding fibrous tissue. Most of the replicated stem cells are then pushed out of the duplication areas into the maturation zones (i.e., lateral portion of the gland crypts) by the volume of replicated cells. In the maturation zones that are subjected to the effect of maturation factor, the duplication mitosis of stem cells is converted to maturation mitosis by the maturation factor also derived
Received 25 June 2001 Accepted 13 February 2002 Correspondence to: Yoso Hirata MD, Hirata Hospital, 5-4-23 Hommachi, 780-0870 Kochi, Nippon, Japan. Phone: +81-888-75-6221; Fax: +81-888-713801; E-mail: [email protected]
630
from the nearest fibrous tissue supporting the zones. Through a prescribed number of maturation mitotic phases, the displaced stem cells gradually mature, or differentiate, into a predetermined number of terminally matured functional end cells with a prescribed life span, and thus comprise the functional areas of the mucous layer. These functional end cells eventually die, and are then replaced by the subsequent generations of terminal end cells. This cell turnover is continuous and maintains constant volume of functional cells in the mucous layer. The duplication mitosis of the stem cells remaining in the duplication areas supplies cells to the maturation zones while also supplying cells to the duplication areas, thus establishing the histological identity and continuity of the gastric mucosa. Conversely, the maturation mitosis does not contribute to establishing the histological identity and continuity.
PHYSIO-MITOTIC DEVELOPMENTS AND FIBROUS TISSUES In the example of gastric mucosa, the factor regulating the duplication areas is specifically derived from fibrous
Mesoderm layer
631
Fig. 1 Gastric mucous layer (Glandula).
Fig. 2 Two types of mitosis in the gland crypt.
tissues in direct contact with the areas. The maturation zones and all sites outside of the duplication areas are constantly subjected to the effect of maturation factor, which is also derived from the nearest supporting fibrous tissues. Consequently, the two types of mitosis occurring in the gland crypts are maintained by the two different factors, which are secreted concomitantly from ª 2002 Elsevier Science Ltd. All rights reserved.
the supporting fibrous tissues themselves. Thus the gastric mucosa is maintained by the fibrous tissues, and is supported by capillary beds found within the fibrous tissues. In principle, all histological organizations include fibrous support tissues, and these fibrous tissues regulate and preserve normal mitotic conditions by producing the duplication and maturation factors. These Medical Hypotheses (2002) 59(6), 630–635
632 Hirata and Hirata
essential fibrous tissues differentiated during embryogenesis since the three germ layers are derived from the blastula. DIFFERENTIATION OF MESODERM LAYER During the first embryological mitotic duplications, a fertilized cell replicates and forms a spherical blastula (Fig. 3). When the blastula reaches a certain size, some of the cells migrate into the blastula sphere. These cells then differentiate into the mesodermal cells under the influence of the surrounding blastula cells. As these mesodermal cells continue to replicate through duplication mitosis, the first effect of maturation factor is exerted from the cells themselves, and functions to convert the duplication mitosis of blastula cells into the first matu-
ration (i.e., differentiation) mitosis within the blastula sphere. The resultant cells then invaginate into the blastula, and are thus surrounded by mesoderm forming the endodermal germ layer. The remaining blastula cells in contact with the external surface of the mesoderm layer then differentiate into the third germ layer, the ectoderm, without migrating into the blastula. Thus, formation of the three germ layers is accomplished (Fig. 3). Throughout the process, the mesoderm layer differentiated first, and initiated the formation of all three germ layers. The duplication mitosis within the mesoderm layer constitutively produces a maturation factor, which might convert duplication mitosis to maturation within the ectoderm and endoderm layers. Through the converted maturation mitosis, the duplication factor for the mesoderm layer is synergistically produced from the
Fig. 3 Diagram showing formation of the three germ layers.
Medical Hypotheses (2002) 59(6), 630–635
ª 2002 Elsevier Science Ltd. All rights reserved.
Mesoderm layer
ectoderm and endoderm layers. Conversely, the duplication mitosis within the ectoderm and endoderm layers produces the antagonistic maturation factor for the mesoderm layer. Consequently, the mesoderm layer and the ectoderm and endoderm have antagonistic and synergistic interactions. During these complex mitotic developments, each germ layer creates its own maturation conditions involving a large number of duplication areas. During the mitosis of the differentiating mesoderm layer, each of the duplication areas surrounded by the maturation zones is invaginated into the mesoderm layer to form a histological structural unit of differentiation (Fig. 4). Since the mesoderm surrounding the
633
structural units was the first germ layer to differentiate in the blastula, it alone initiates the formation of the structural units comprising the germ layers, while continually providing the duplication and maturation factors. Accordingly, the genesis and degeneration of the structural units is controlled by the mitotic conditions of the surrounding mesoderm layer. In summary, all developing functional tissues, including various hemocytoblasts differentiated from the mesoderm, require the fibrous support tissues that are also differentiated from mesoderm through mesenchyme. During differentiation from individual germ layers to functional tissues, a large number of the structural units
Fig. 4 Diagram showing the embryological differural unit of the intestinal mucosal tissue.
ª 2002 Elsevier Science Ltd. All rights reserved.
Medical Hypotheses (2002) 59(6), 630–635
634 Hirata and Hirata
Fig. 5 Diagram showing the segmentation of structural unit.
comprising individual germ layers must be gradually differentiated into functional tissues. These differentiated structural units are always surrounded by fibrous support tissues, which regulate them by concomitantly producing antagonistic duplication and maturation factors.
ESSENTIAL ROLE OF FIBROUS TISSUES As previously described by Hirata (6), in the example of intestinal mucosa, a prescribed volume of functional end cells is produced from a single duplication areas (i.e., basal portions of a gland crypt). This volume of cells forms the structural units of the entire functional
Fig. 6 Diagram showing the degeneration of a structural unit.
Medical Hypotheses (2002) 59(6), 630–635
ª 2002 Elsevier Science Ltd. All rights reserved.
Mesoderm layer
mucous tissue (Fig. 4). Consequently, an increase in the number of duplication areas that may result from an over-production of the duplication factor by the supporting fibrous tissues may cause a progressive increase in growth of the functional mucosa (Fig. 5). Conversely, degeneration of the duplication areas may result from replacement of the duplication factor by maturation factor produced by other fibrous tissues, and may gives rise to a progressive decrease in the growth of the functional mucosa (Fig. 6). This fluctuation in the number of duplication areas is dependent on the mitotic activity within these areas, reflected in the density of structural units comprising the functional tissues. These structural units (Fig. 4) are each surrounded by fibrous support tissues, derived from mesoderm that produces the different duplication and maturation factors. Although the mitosis occurring in these fibrous tissues might not be identifiable as duplication or maturation types, the fibrous tissues, may consist of two physio-mitotic layers: the maturation and duplicative layers. The maturation layers are juxtaposed on the duplication areas and provide the duplication factor. In contrast, the duplication layers support the maturation zones surrounding the areas and produce the maturation factor, which may initiate and regulate the progression from stem cell to functional end cell while also regulating the functional areas outside of the duplication areas. Throughout these mitotic progressions, a large number of histological structural units, with their fibrous support tissues, are maintained at a given volume within the tissues by the intrinsic ability of the supporting fibrous tissues, to exert concomitantly the two different effects of duplication and maturation factors. Since the three germ layers are derived from the blastula, through the fluctuations in the number of the structural units, every functional tissue would individually differentiate from one of the three germ layers. CONCLUSION The fibrous tissues that differentiate from mesoderm while enveloping the histological structural units within tissues are responsible for initiating the differentiation from the three germ layers to the functional tissues. Following differentiation, the fibrous support tissues continue to play an essential role in regulating the mitotic conditions of these structural units by concomitantly producing the antagonistic duplication and maturation factors. Consequently, to regulate the functional tissues, the fibrous support tissues have two
ª 2002 Elsevier Science Ltd. All rights reserved.
635
functional layers: the duplication layers which secrete the maturation factor in the maturation zones, and the maturation layers, which secrete the duplication factor for the stem cells within the duplication areas. Thus, all functional tissues maintain a constant volume of cells through maintaining the appropriate mitotic conditions. Consequently, the fibrous support tissues play an essential role in maintaining the physio-mitotic conditions of normally functioning tissues, in addition to supporting the histological organization that includes capillary beds investing the fibrous tissues themselves. However, in reality, certain diseases develop due to an imbalance in the mitotic conditions. As described by Hirata (1–4), cancer development may physio-mitotically be dependent on a certain cellular peculiarity interfering with the effect of maturation factor provided by fibrous tissues. Leukemia development may also be dependent on a general deterioration in the effect of maturation factor for leuko-blastcysts, without depending on a certain cellular defect in the maturability of individual leuko-blastcysts (5–7). However, various other diseases including fibro-multiplastic, myoatrophic, and neuroatrophic diseases may also develop due to some imbalance in mitotic interaction between the fibrous and functional tissues. Proper balance might be restored through the use of either duplication or maturation factors that would interact with the fibrous and functional cells. This approach may be the most important step in eradicating these diseases.
REFERENCES 1. Hirata Y. Duplication mitosis in epithelio-glandular tissue. Med Hypotheses 1992; 37: 44–46. 2. Hirata Y. Hetero-duplication type of cancerous mitosis. Med Hypotheses 1993; 41: 509–512. 3. Hirata Y. Established histological identity and cell destruction treatment for cancer. Med Hypotheses 2000; 55(1): 15–23. 4. Hirata Y. A physio-mitotic theory and new concept of cancer development. Med Hypotheses 2002; 58(5): 361–364. 5. Hirata Y. A physio-mitotic theory and new concept of leukemia development. Med Hypotheses 2002; 58(4): 251–253. 6. Hirata Y. A physio-mitotic theory and new concept of embryo-logical differentiation. Med Hypotheses 2002; 58(5): 365–368. 7. Hirata Y. Leukemia eradication and the effect of maturation factor. Med Hypotheses 2002; 58(5): 369–370.
Medical Hypotheses (2002) 59(6), 630–635